Cancer is a multifaceted disease characterized by the uncontrolled growth and spread of abnormal cells in the body. It can originate almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and divide to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place. Cancer disrupts this orderly process. As cells become more abnormal, old or damaged cells survive when they should die, and new cells form when they are not needed. These extra cells can divide without stopping and may form growths called tumours.
There are more than 100 types of cancer, classified by the type of cell that is initially affected. Major categories include:
• Carcinoma: Carcinoma is a type of cancer that starts in the cells that make up the skin or the tissue lining organs, such as the liver, kidneys, or lungs. These cells, known as epithelial cells, cover the inside and outside surfaces of the body. Carcinoma is the most common form of cancer, accounting for the majority of cancer diagnoses. Carcinomas are classified based on the type of epithelial cell they originate from and their appearance under a microscope. Adenocarcinoma originates in the glandular tissue or cells of the epithelium (the layer of cells covering the body’s surface and lining internal organs and glands). It commonly affects organs like the breast, colon, prostate, and lungs. Squamous Cell Carcinoma begins in the squamous cells, which are flat, thin cells that make up the skin’s outer layer and the mucous membranes lining some body parts. This type of carcinoma is often found in the lungs, skin, and lining of the digestive tract. Basal Cell Carcinoma is the most common form of skin cancer, arising from the basal cells located at the bottom of the epidermis (the outermost skin layer). It is usually caused by long-term exposure to UV radiation from sunlight. Transitional Cell Carcinoma starts in the transitional epithelium (urothelium), found in the lining of the bladder, ureters, part of the kidneys (renal pelvis), and a few other organs. This type of carcinoma is also referred to as urothelial carcinoma.
• Sarcoma: Sarcoma is a type of cancer that originates in the bones and soft tissues of the body, including muscles, fat, blood vessels, lymph vessels, and fibrous tissues (such as tendons and ligaments). Unlike carcinomas, which are cancers that begin in the skin or tissue linings of internal organs and are more common, sarcomas are relatively rare. Sarcomas are divided into two main categories: bone sarcomas (osteosarcomas) and soft tissue sarcomas. Bone Sarcomas (Osteosarcomas) affect the bones and are more common in children and young adults, often occurring in the bones of the legs or arms. Soft Tissue Sarcomas are a diverse group of cancers that arise in the body’s soft tissues. Liposarcoma originates in fat cells. Leiomyosarcoma develops in smooth muscle tissue. Rhabdomyosarcoma begins in skeletal muscle tissue. Angiosarcoma starts in the blood vessels’ lining. Synovial Sarcoma originates in the tissues around joints.
• Leukaemia: Leukaemia is a type of cancer that affects the blood and bone marrow, the soft tissue inside bones where blood cells are produced. It is characterized by the rapid production of abnormal white blood cells, which are crucial to the body’s immune response. These abnormal cells can’t perform their normal functions and start to outnumber healthy blood cells, impairing the body’s ability to fight infection and causing damage to other organs. Leukaemia is primarily categorised into four main types, based on the speed of progression (acute or chronic) and the type of blood cell affected (lymphoid or myeloid). Acute Lymphoblastic Leukaemia (ALL) rapidly progresses and affects lymphoid cells. It is the most common type of leukaemia in children, though it also affects adults. Acute Myeloid Leukaemia (AML) also progresses quickly but affects myeloid cells. It occurs in both children and adults. Chronic Lymphocytic Leukaemia (CLL) develops slowly and affects lymphoid cells. It is most common in adults over the age of 55. Chronic Myeloid Leukaemia (CML) progresses slowly at first and affects myeloid cells. It mostly occurs in adults.
• Lymphoma: Lymphoma is a cancer of the lymphatic system, which is part of the body’s germ-fighting network. It primarily affects lymphocytes, a type of white blood cell that plays a crucial role in the immune response. Lymphoma can occur in various parts of the body, including the lymph nodes, spleen, bone marrow, and other organs. Hodgkin Lymphoma (HL) characterized by the presence of Reed-Sternberg cells, it is distinguished from other lymphomas by certain unique features. Hodgkin lymphoma can affect people of any age but is most common in young adults (ages 20-30) and older adults (over 55). Non-Hodgkin Lymphoma (NHL) is a larger group of blood cancers that includes all other types of lymphoma. NHL can range from slow growing to very aggressive and can affect lymphocytes at any stage of development.
* Myeloma: Myeloma, also known as multiple myeloma, specifically affects plasma cells, a type of white blood cell found in the bone marrow that produces antibodies. This cancer leads to an overproduction of abnormal plasma cells, which can damage the bones and interfere with the production of normal blood cells and immune function. Common signs and symptoms of myeloma include bone pain, especially in the spine or chest, nausea, constipation, loss of appetite, mental fogginess or confusion, fatigue, frequent infections, and weight loss. Because the abnormal plasma cells produce abnormal antibodies that can damage the kidneys, patients may also experience kidney problems.
• Central Nervous System Cancers: Central Nervous System (CNS) cancers refer to a group of malignancies that originate in the tissues of the brain or spinal cord, which together make up the central nervous system. These cancers are characterized by the uncontrolled growth of cells within the CNS, which can interfere with its essential functions, including controlling movement, thought processes, and the regulation of many bodily functions. CNS cancers include a wide variety of tumours, classified based on the type of cells from which they originate. Gliomas are tumours that arise from glial cells, which provide support and nutrition to the central nervous system. Gliomas are categorized into several types, including astrocytomas, oligodendrogliomas, and glioblastomas, with glioblastoma being the most aggressive form. Meningiomas are tumours that form in the meninges, the protective membranes that cover the brain and spinal cord. Meningiomas are usually benign but can be malignant in rare cases. Schwannomas are tumours that develop from Schwann cells, which are responsible for the myelin sheath that protects nerve fibres. Schwannomas are typically benign. Medulloblastomas is a type of cancer more commonly found in children, originating in the cerebellum, the part of the brain that controls balance and movement.
The exact cause of cancer is not always clear, but several risk factors have been identified that increase an individual’s chances of developing cancer, including:
• Genetic Factors: Family history, inheritance, and genetic mutations such as BRCA1 and BRCA2.
• Lifestyle Factors: Tobacco use, excessive alcohol consumption, poor diet, physical inactivity, and obesity.
• Environmental Exposure: Exposure to harmful substances such as asbestos, benzene, and radiation.
• Infections: Certain infections can increase the risk, such as human papillomavirus (HPV), hepatitis B, hepatitis C, and Helicobacter pylori.
Diagnosis typically involves a combination of imaging tests (like MRIs, CT scans, and X-rays), laboratory tests (including blood tests and biopsies), and genetic tests. Once cancer is diagnosed, staging tests are performed to find out the extent of cancer in the body and help guide treatment options.
Cancer treatment depends on the type, stage, and how advanced it is. Treatments may include:
• Surgery: To remove as much of the cancer as possible.
• Chemotherapy: Uses drugs to kill cancer cells.
• Radiation Therapy: Uses high-energy rays to kill cancer cells.
• Immunotherapy: Helps your immune system fight cancer.
• Targeted Therapy: Targets the changes in cancer cells that help them grow, divide, and spread.
• Hormone Therapy: Treats cancers that use hormones to grow.
Ongoing research and clinical trials are crucial for understanding cancer and finding new and better ways to treat it. Advances in genomics, immunotherapy, and personalized medicine are changing the landscape of cancer treatment, offering new hope to patients. Cancer is a complex group of diseases with varying causes and treatments. The battle against cancer involves prevention, early detection, effective treatment, and ongoing research. With continued advancements in science and medicine, there is hope for more effective treatments and ultimately, cures for different types of cancer.
GENETIC FACTORS INVOLVED IN CANCER
Involvement of genetic factors in cancer development is both complex and multifaceted, encompassing inherited mutations, acquired mutations throughout a person’s life, and genetic susceptibility that increases the risk of developing cancer. Here, we delve into these aspects to understand how genetics play a crucial role in cancer.
Some cancers are known to run in families due to mutations in specific genes that are passed from one generation to the next. These inherited mutations do not mean cancer is inevitable but indicate a higher risk of developing the disease.
Mutations in these BRCA1 and BRCA2 genes significantly increase the risk of breast and ovarian cancers. Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer – HNPCC) is caused by mutations in genes that repair DNA mismatches, leading to a higher risk of colorectal cancer and other cancers. Familial adenomatous polyposis (FAP) is an inherited condition associated with a mutation in the APC gene, leading to the development of numerous polyps in the colon and rectum and a high risk of colorectal cancer.
The majority of cancers are caused by mutations acquired during a person’s life rather than inherited mutations. These can result from exposure to carcinogens like tobacco smoke, radiation, certain chemicals, and viruses. Cells may also acquire mutations as a result of errors that occur as DNA is copied during cell division or due to the influence of hormones, obesity, inflammation, and other factors.
Some individuals may have a genetic susceptibility that makes them more prone to cancer when exposed to certain environmental factors. This susceptibility can be due to variations in genes involved in detoxifying harmful substances, DNA repair, or the immune response.
The field of genomics has significantly advanced our understanding of the genetic basis of cancer. It involves the study of a person’s genome to identify genetic differences, including mutations that can lead to cancer. Key areas include Oncogenes are genes that, when mutated, have the potential to cause normal cells to become cancerous. Examples include HER2 in some breast cancers. Tumor Suppressor Genes are that normally prevent cancer by controlling cell growth and repair. Mutations in these genes, such as TP53, can lead to cancer.
Identifying genetic mutations in a cancer patient’s tumour can guide the selection of targeted therapies, which are drugs that specifically attack cancer cells by interfering with the mutated molecules that promote their growth. Understanding the genetic factors involved in cancer presents both challenges and opportunities. While identifying genetic risk factors can lead to strategies for early detection, prevention, and targeted treatment, it also raises ethical and psychological concerns regarding genetic testing and counselling.
Research in cancer genomics is rapidly advancing, offering hope for more precise and personalized cancer treatments. By focusing on the genetic and molecular changes that drive cancer, researchers aim to develop new treatments that specifically target these changes, improving outcomes for patients.
PATHOPHYSIOLOGY OF CANCERS
The pathophysiology of cancer involves understanding the processes and mechanisms through which cancer develops and progresses in the body. This encompasses the transformation of normal cells into cancerous cells, their proliferation, invasion into surrounding tissues, and eventual spread to other parts of the body (metastasis). At the heart of cancer pathophysiology are genetic and molecular alterations that disrupt normal cell function, leading to uncontrolled cell growth and tumour formation. Here’s an overview of these key processes:
Cancer begins with changes (mutations) in the DNA of a cell. These mutations can affect different types of genes, including:
• Oncogenes: Normally promote cell growth and division. Mutations can turn them into a form that over-activates cell growth.
• Tumor Suppressor Genes: Normally regulate cell division and ensure the integrity of the genome. Mutations can inactivate these functions, leading to uncontrolled cell growth.
• DNA Repair Genes: Normally fix the errors in DNA replication. Mutations can lead to increased DNA errors and instability, contributing to cancer progression.
As a result of these mutations, cells begin to grow and divide uncontrollably. This unregulated growth can lead to the formation of a mass of tissue, known as a tumour. Tumours can be benign (non-cancerous) or malignant (cancerous). Malignant tumours can invade nearby tissues and organs, a process known as invasion.
For a tumour to grow beyond a certain size, it needs a blood supply. Cancer cells can secrete substances that stimulate angiogenesis, the formation of new blood vessels. This process provides the tumour with the oxygen and nutrients it needs to continue growing.
Cancer cells can break away from the original (primary) tumour, invade neighbouring tissues, and enter the bloodstream or lymphatic system. This allows them to travel to distant parts of the body and form new (secondary) tumours, a process known as metastasis. Metastasis is a hallmark of cancer and is often the cause of death from the disease.
Cancer cells have various mechanisms to evade detection and destruction by the immune system. For example, they can express proteins on their surface that turn off immune cells. They can also create an environment around the tumour (tumor microenvironment) that suppresses the immune response.
Cancer cells often alter their energy metabolism to support their rapid growth and division. This phenomenon, known as the Warburg effect, involves cancer cells favouring glycolysis for energy production, even in the presence of oxygen (aerobic glycolysis). This metabolic reprogramming supports the biosynthetic needs of rapidly dividing cells and contributes to the progression of cancer.
The pathophysiology of cancer is complex, involving multiple genetic, molecular, and cellular processes that enable cells to grow uncontrollably, invade nearby tissues, and spread to other parts of the body. Understanding these mechanisms is crucial for developing targeted therapies and interventions to prevent cancer progression and improve patient outcomes. Ongoing research continues to unravel the intricacies of cancer pathophysiology, offering hope for more effective treatments in the future.
ROLE OF HORMONES IN CANCER
Hormones, which are chemical messengers that regulate processes in the body, can play significant roles in the development and progression of certain cancers. They can influence cell growth directly by acting on hormone-sensitive tissues or indirectly by affecting the production of growth factors. The association between hormones and cancer is particularly evident in breast, prostate, ovarian, and endometrial cancers.
Oestrogen and Progesterone can stimulate the growth of hormone-receptor-positive breast and endometrial cancer cells. These hormones bind to their respective receptors, ER and PR, which are transcription factors that regulate the expression of genes involved in cell division and growth. In breast cancer, oestrogen is a primary driver in the majority of cases, particularly those classified as ER-positive. Target Molecules: Oestrogen Receptor (ER) and Progesterone Receptor (PR).
Androgens, such as testosterone and dihydrotestosterone (DHT), promote the growth of prostate cells. In prostate cancer, androgens bind to the AR, stimulating the growth of cancer cells. Androgen deprivation therapy, which reduces androgen levels or blocks their action on cancer cells, is a common treatment for advanced prostate cancer. Target Molecule: Androgen Receptor (AR).
Insulin and Insulin-like Growth Factors can promote cell growth and survival. High levels of insulin (often associated with obesity and type 2 diabetes) and IGFs have been linked to an increased risk of several cancers, including breast, colorectal, and pancreatic cancers. These hormones bind to their receptors, triggering signalling pathways that promote cell division and inhibit apoptosis (programmed cell death). Target Molecules: Insulin Receptor (IR) and Insulin-like Growth Factor 1 Receptor (IGF1R).
Gonadotropins including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are involved in the stimulation of ovarian follicles. High levels of gonadotropins, which can occur in postmenopausal women, have been suggested to play a role in the development of ovarian cancer through overstimulation of the ovaries. Target Molecules: Gonadotropin Receptors (LH and FSH receptors).
Hormones can significantly influence the risk, development, and progression of certain cancers by acting on specific target molecules, mainly hormone receptors. The understanding of these mechanisms has led to the development of hormone therapies that target these pathways, such as selective oestrogen receptor modulators (SERMs) for breast cancer, androgen deprivation therapy for prostate cancer, and hormone suppressive therapies in gynaecological cancers. Ongoing research continues to explore how hormonal imbalances contribute to cancer and to develop new treatments that target these processes.
ENZYME SYSTEMS INVOLVED IN CANCER
Cancer cells manipulate various enzyme systems to support their uncontrolled growth, survival, invasion, and metastasis. These enzymes are involved in diverse biological processes, including DNA replication, cell cycle progression, apoptosis, metabolism, and the remodelling of the extracellular matrix. Understanding these enzyme systems, their substrates, activators, and inhibitors is crucial for developing targeted cancer therapies.
Telomerase enzyme. Substrate: Telomers, the protective caps at the end of chromosomes. Activators: Cancer cells often activate telomerase expression through mutations in regulatory genes, allowing them to maintain telomere length and achieve cellular immortality. Inhibitors: Telomerase inhibitors (e.g., Imetelstat) are being explored as potential cancer treatments by preventing the indefinite proliferation of cancer cells.
Topoisomerases. Substrate: DNA strands; these enzymes relieve torsional stress during DNA replication and transcription by causing temporary breaks in the DNA. Activators: Cancer cells frequently exhibit increased expression of topoisomerases to support rapid cell division. Inhibitors: Topoisomerase inhibitors, such as Topotecan (Topo I inhibitor) and Etoposide (Topo II inhibitor), are used in chemotherapy to induce DNA damage by stabilizing the transient break caused by the enzyme, leading to cell death.
Matrix Metalloproteinases (MMPs). Substrate: Components of the extracellular matrix (ECM); MMPs degrade various ECM proteins, facilitating tumour invasion and metastasis. Activators: Tumour microenvironment factors such as growth factors, inflammatory cytokines, and cellular stresses can induce MMP expression. Inhibitors: Marimastat is an example of an MMP inhibitor, although clinical success has been limited due to side effects and the complexity of MMP regulation.
Extracellular matrix (ECM) proteins play a critical role in tissue and organ structure and function, essentially forming the complex network that supports cells within tissues. The ECM provides not just physical scaffolding for cells but also influences their development, behaviour, and physiology. The composition of the ECM varies between different tissues, reflecting the specific needs and functions of those tissues. Collagens are the most abundant proteins in the ECM, which provide tensile strength and rigidity to tissues. They are crucial for the structure of skin, bone, tendons, and ligaments. Over 28 types of collagens have been identified, each with a role in different tissues and organs. Elastins are proteins that give tissues their elastic properties, allowing them to stretch and then return to their original shape. Elastins are particularly important in tissues that undergo repeated stretching, such as blood vessels, lungs, and skin. Fibronectins are glycoproteins that help cells attach to the extracellular matrix. Fibronectins play a critical role in wound healing, embryonic development, and blood clotting. They act as a sort of bridge between cells and the ECM, influencing cell shape, movement, and differentiation. Laminins are high-molecular-weight proteins that are essential components of the basal lamina, a specialized layer of the ECM found at the base of epithelial tissues. Laminins are crucial for cell adhesion, differentiation, migration, and survival. Proteoglycans are made of a core protein with one or more covalently attached glycosaminoglycan (GAG) chain(s). Proteoglycans fill the spaces between cells in the ECM, contributing to its hydration and resistance to compression. They also play roles in cell signalling. Glycosaminoglycans (GAGs), although not proteins themselves, are long, unbranched polysaccharides that attach to core proteins to form proteoglycans. Examples include hyaluronan, chondroitin sulphate, and heparin sulphate. They contribute to the ECM’s physical properties, such as resistance to pressure and hydration. The ECM is dynamic and constantly remodelled by the cells that reside within it. This remodeling is crucial during development, wound healing, and in response to environmental changes. However, dysregulation of ECM remodelling is implicated in various diseases, including fibrosis, cancer, and inflammatory conditions, highlighting the importance of ECM proteins in both health and disease.
Cyclin-dependent Kinases (CDKs. Substrate: Various proteins involved in cell cycle progression, particularly those regulating the transition from the G1 phase to the S phase of the cell cycle. Activators: Cyclins (regulatory proteins that ensure the proper timing of cell cycle progression) activate CDKs. Inhibitors: CDK inhibitors like Palbociclib target specific CDKs to halt the proliferation of cancer cells by preventing cell cycle progression.
Poly (ADP-ribose) Polymerase (PARP). Substrate: DNA; PARP enzymes are involved in DNA repair processes. Activators: DNA damage activates PARP to facilitate DNA repair. Inhibitors: PARP inhibitors, such as Olaparib, exploit the concept of synthetic lethality in cancer cells deficient in other DNA repair pathways (e.g., BRCA1/2 mutations) by further impairing DNA repair, leading to cell death.
Protein Kinase B (Akt). Substrate: Multiple downstream targets involved in cell survival, growth, proliferation, and metabolism. Activators: Phosphoinositide 3-kinase (PI3K) activation leads to Akt activation, a pathway frequently upregulated in cancer. Inhibitors: Akt inhibitors, such as Ipatasertib, are being developed to target this key signalling pathway in cancer cells.
These enzyme systems play critical roles in cancer development and progression by supporting the hallmark capabilities of cancer cells. Targeting these enzymes and their associated pathways has been a significant focus of cancer drug development, leading to the introduction of several effective treatments. Continued research into the complex roles of these enzymes in cancer will likely yield new therapeutic targets and strategies.
HEAVY METALS AND MICROELEMENTS
Heavy metals and microelements have complex roles in cancer, acting either as potential carcinogens or as essential nutrients that, when imbalanced, can contribute to cancer development. The distinction between their beneficial and harmful effects often depends on their concentration and bioavailability in the body.
Several heavy metals are recognized as carcinogens. They can contribute to cancer development through various mechanisms, including direct DNA damage, oxidative stress induction, and interference with DNA repair processes.
Chronic exposure to arsenic, often through contaminated water, is associated with an increased risk of skin, lung, and bladder cancers. Arsenic induces oxidative stress and may interfere with cellular signalling and DNA repair mechanisms.
Found in tobacco smoke and some industrial environments, cadmium exposure is linked to prostate, lung, and kidney cancers. Cadmium can cause oxidative stress and mimic the effects of estrogens, promoting the growth of hormone-sensitive cancers.
Occupational exposure to hexavalent chromium compounds is associated with lung cancer. Chromium (VI) can produce free radicals, leading to DNA damage.
Although its mechanism is less clear, lead exposure has been suggested to increase the risk for brain, lung, stomach, and kidney cancers among others. It might affect gene expression and mimic the action of calcium, interfering with cell signaling.
Microelements, or trace elements, are essential nutrients required in small amounts for various physiological functions. Imbalances (either deficiency or excess) in these elements can influence cancer risk and progression.
While essential for various cellular functions, excess iron can contribute to the formation of free radicals, leading to oxidative stress and potential DNA damage. Iron overload conditions, such as hemochromatosis, have been linked to an increased risk of liver cancer and other cancers.
Selenium has antioxidant properties and is thought to protect against cancer by preventing oxidative damage to DNA and other cellular components. Selenium deficiency has been associated with an increased risk of certain cancers, whereas adequate selenium levels might have a protective effect.
Zinc plays a crucial role in DNA synthesis, cell division, and immune function. Zinc deficiency can impair the immune response and potentially increase susceptibility to cancer. However, the relationship between zinc and cancer risk is complex and not fully understood.
Copper is essential for angiogenesis and immune function. While necessary in small amounts, excessive copper levels might promote angiogenesis and tumour growth.
The relationship between heavy metals, microelements, and cancer is intricate, with both groups capable of influencing cancer risk and progression in varying ways. For heavy metals, the carcinogenic potential is a significant concern, emphasizing the importance of monitoring and limiting exposure to these substances. For microelements, maintaining a balanced intake is crucial, as both deficiencies and excesses can contribute to cancer development. Ongoing research is essential to fully understand these relationships and to develop strategies for prevention and treatment based on modifying exposure to these elements.
ACIDITY OF CELLULAR MICROENVIRONMENT
The acidity of the cellular microenvironment plays a significant role in cancer development, progression, and metastasis. Cancer cells exhibit altered metabolism that leads to an acidic microenvironment, which can affect tumor growth, invasion, and resistance to therapies. This alteration is primarily due to the Warburg effect, a metabolic shift in cancer cells where they preferentially use glycolysis for energy production, even in the presence of oxygen. This process is less efficient than oxidative phosphorylation, leading to the increased production of lactate and protons, thus acidifying the tumour microenvironment.
The acidic microenvironment aids in tumor invasion and metastasis in several ways. Acidic conditions activate enzymes such as cathepsins and matrix metalloproteinases (MMPs), which degrade the extracellular matrix (ECM). This degradation facilitates tumour cell invasion into surrounding tissues and vasculature, aiding metastasis. The acidic microenvironment promotes the expression of genes associated with increased motility and invasiveness of cancer cells, further enhancing their ability to metastasize.
Acidity in the tumour microenvironment can suppress the immune response against cancer cells. Acidic conditions can inhibit the function of various immune cells, including T cells and natural killer (NK) cells, reducing their ability to attack tumor cells. It can also promote the development of immune-suppressive cells like myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), which further protect the tumour from the immune response. The acidic environment can lead to changes in the expression of immune checkpoint molecules and antigens on tumour cells, affecting their recognition by the immune system.
Acidic conditions can affect the uptake, distribution, and efficacy of chemotherapeutic agents. Many drugs are less effective or inactive in acidic conditions, and the altered pH gradient between the inside and outside of cancer cells can reduce drug accumulation in tumor cells. The low pH environment can confer resistance to radiation therapy by affecting DNA repair mechanisms and reducing the production of reactive oxygen species (ROS) generated by radiation, which are crucial for its cytotoxic effects.
Cancer cells can adapt to and even thrive in acidic conditions. The acidification of the tumour microenvironment can promote genetic and phenotypic changes in cancer cells that enhance their survival, proliferation, and metabolic flexibility. The acidic microenvironment can act as a selection pressure, favouring more aggressive cancer cells that are better adapted to these conditions. This selective pressure can lead to the emergence of more malignant tumour phenotypes.
The acidity of the cellular microenvironment is a hallmark of cancer that contributes to tumor progression, invasion, immune evasion, and therapy resistance. Understanding the mechanisms by which acidity influences cancer dynamics offers potential targets for therapeutic intervention. Strategies to modulate the tumor pH, either by buffering the acidity or targeting the metabolic pathways leading to acid production, are being explored as potential cancer treatments. These approaches aim to not only directly inhibit tumour growth but also improve the efficacy of existing therapies and the immune response against tumours.
ROLE OF HYPERACTIVE SUPEROXIDES
Hyperactive superoxides and other reactive oxygen species (ROS) play a dual role in cancer, acting both as promoters of tumour development and progression, and, under certain conditions, as agents that can damage cancer cells. Superoxides, specifically, are a type of ROS that are molecules containing oxygen with an extra electron, making them highly reactive. The balance between the production and elimination of ROS within cells is crucial for maintaining cellular homeostasis. In cancer, this balance is often disrupted, leading to elevated levels of ROS, including superoxides.
High levels of superoxides can cause direct damage to DNA, including strand breaks and base modifications. This damage can lead to mutations and genomic instability, a hallmark of cancer.
Superoxides and other ROS can act as signalling molecules, altering cellular signal transduction pathways. They can activate pathways that promote cell proliferation, such as the MAPK and PI3K/AKT pathways, and inhibit pathways that cause cell death, promoting tumor growth and survival.
Elevated ROS levels can stimulate the formation of new blood vessels (angiogenesis) by upregulating pro-angiogenic factors like VEGF (vascular endothelial growth factor). Angiogenesis is essential for tumour growth and metastasis, providing the tumour with nutrients and oxygen. ROS can promote the invasion and metastasis of cancer cells by inducing the expression of MMPs (matrix metalloproteinases), which degrade the extracellular matrix, and by encouraging the epithelial-mesenchymal transition (EMT), a process whereby cancer cells gain migratory and invasive properties.
Although low to moderate levels of ROS can promote tumour growth, very high levels of ROS are toxic to cells, including cancer cells, and can induce cell death through apoptosis or necrosis. Cancer cells, due to their altered metabolism and rapid growth, have higher intrinsic oxidative stress than normal cells. Therapeutic strategies that further increase ROS levels specifically in cancer cells can push them over the threshold of tolerable stress, leading to cell death while sparing normal cells.
Understanding the role of superoxides and other ROS in cancer has therapeutic implications. While antioxidants can scavenge ROS and protect cells from oxidative damage, their role in cancer therapy is complex. Antioxidants might prevent initial DNA damage and cancer development; however, in established cancers, they might protect cancer cells from ROS-induced cell death.
Therapies that increase ROS levels, particularly in cancer cells, can promote cancer cell death. This approach can be particularly effective in combination with treatments that selectively increase oxidative stress in cancer cells beyond their survival threshold.
Inhibiting enzymes that contribute to ROS production in cancer cells, such as NADPH oxidases, or targeting mitochondrial dysfunction, can reduce ROS levels and inhibit cancer progression.
The role of hyperactive superoxides and other ROS in cancer is multifaceted, contributing to cancer initiation, progression, and the acquisition of malignant traits. However, this same property can be exploited for therapeutic purposes, aiming to selectively kill cancer cells by tipping their delicate oxidative balance. Ongoing research into the specific mechanisms of ROS action in cancer and the development of targeted therapies holds promise for more effective cancer treatments.
PHYTOCHEMICALS AND CANCER
Phytochemicals are bioactive compounds found in plants that have been increasingly recognized for their potential anti-cancer properties. These naturally occurring substances are part of plants’ defence mechanisms but also offer protective health benefits when consumed by humans. Phytochemicals encompass a wide range of compounds, including flavonoids, carotenoids, glucosinolates, and polyphenols, among others. Their anti-cancer effects are attributed to various mechanisms, including antioxidant activity, modulation of detoxification enzymes, regulation of hormone metabolism, anti-inflammatory effects, and the ability to interfere with the processes of cancer cell proliferation, apoptosis (programmed cell death), angiogenesis (formation of new blood vessels), and metastasis (spread of cancer cells to other parts of the body).
Many phytochemicals possess strong antioxidant properties, allowing them to neutralize free radicals and reactive oxygen species (ROS) in the body. This reduces oxidative stress and prevents oxidative damage to cells’ DNA, proteins, and lipids, potentially lowering the risk of mutation and cancer development.
Phytochemicals can influence the activity of phase I and phase II detoxification enzymes. By enhancing phase II enzyme activity, phytochemicals increase the detoxification and elimination of potential carcinogens from the body. Conversely, they can inhibit phase I enzymes, which are often involved in the activation of pro-carcinogens.
Certain phytochemicals, such as those found in soy (isoflavones like genistein), can modulate hormone metabolism. They exert weak estrogenic or anti-estrogenic effects by binding to oestrogen receptors, potentially reducing the risk of hormone-related cancers like breast and prostate cancer.
Inflammation is a critical component of tumour progression. Many phytochemicals have anti-inflammatory properties that can disrupt cancer development. For example, curcumin (found in turmeric) is known for its potent anti-inflammatory and anticancer effects, inhibiting the NF-κB pathway, which plays a significant role in inflammatory processes and cancer.
Phytochemicals can inhibit the proliferation of cancer cells and induce apoptosis, thereby reducing tumour growth. Compounds such as resveratrol (found in grapes and berries), sulforaphane (from cruciferous vegetables like broccoli), and epigallocatechin gallate (EGCG, found in green tea) have been shown to affect various signalling pathways involved in cell cycle regulation and apoptosis.
Some phytochemicals can inhibit angiogenesis, the process by which tumours develop their own blood supply to support growth, and metastasis. For instance, flavonoids can suppress the expression of angiogenic factors like VEGF (Vascular Endothelial Growth Factor) and inhibit the enzymes involved in the degradation of the extracellular matrix, which is necessary for cancer cell invasion and metastasis.
The role of phytochemicals in cancer involves a multifaceted approach to preventing and combating the disease. Their ability to target multiple pathways involved in cancer progression makes them promising agents for cancer prevention and, potentially, as adjuncts to conventional cancer therapies. However, while numerous studies support the anti-cancer properties of phytochemicals, further research, particularly clinical trials, is needed to fully understand their efficacy, optimal dosages, and mechanisms of action in humans. Integrating a diet rich in a variety of fruits, vegetables, and whole grains, known sources of phytochemicals, is widely recommended for its potential to reduce cancer risk.
VITAMINS AND CANCER
Vitamins, essential nutrients required for various biochemical and physiological functions, play significant roles in maintaining cellular health and protecting against cancer development. Their roles in cancer are multifaceted, including acting as antioxidants, supporting the immune system, influencing DNA repair, and regulating cell growth and differentiation. While a balanced intake of vitamins through diet is associated with reduced cancer risk for some types, excessive supplementation of certain vitamins has sometimes been linked to increased cancer risk.
Vitamin A (retinol) and its precursor carotenoids (beta-carotene, lycopene) are important for vision, immune function, and cell growth and differentiation. In cancer, they can help regulate cell division and apoptosis, potentially preventing the uncontrolled cell growth characteristic of cancer. High dietary intake of vitamin A and carotenoids has been associated with a reduced risk of certain cancers, including lung and prostate cancer. However, supplementation with high doses of beta-carotene may increase the risk of lung cancer in smokers.
Vitamin C (ascorbic acid) acts as a powerful antioxidant, protecting cells from damage by free radicals and ROS. It also plays a role in collagen formation, supporting the structure of tissues, and enhancing the immune response. While vitamin C’s antioxidant properties suggest a protective role against cancer, studies have shown mixed results. Some research suggests it may lower the risk of cancers such as oesophageal, laryngeal, and pancreatic cancers, especially when consumed through fruits and vegetables rather than supplements.
Vitamin D is essential for bone health, immune function, and cell growth regulation. It exerts anti-cancer effects by promoting cellular differentiation, reducing cancer cell growth, inhibiting angiogenesis, and stimulating apoptosis. Higher levels of vitamin D have been associated with a lower risk of colorectal, breast, and prostate cancers. However, the optimal level of vitamin D for cancer prevention and the potential benefits of supplementation remain under investigation.
Vitamin E is a group of fat-soluble compounds with antioxidant properties. It protects cell membranes from oxidative damage and may also have roles in immune enhancement and inhibition of cancer cell proliferation. Observational studies suggest that higher intake of vitamin E from diet is associated with reduced risk of certain cancers, such as prostate cancer. However, supplementation with high doses of vitamin E has not consistently shown benefits and may, in some studies, increase the risk of other cancers.
Folate (Vitamin B9) is crucial for DNA synthesis and repair and the methylation of DNA, which influences gene expression. Adequate folate intake is essential for maintaining genomic stability and preventing mutations. Adequate dietary folate has been linked to a reduced risk of colorectal, pancreatic, and breast cancers, particularly those associated with alcohol consumption. However, excessive folate intake, especially from supplements, may have complex effects and could potentially increase the risk of certain cancers.
Vitamins play crucial roles in cancer prevention and, potentially, in the adjunctive treatment of cancer by influencing various cellular processes related to cancer development. However, the relationship between vitamin intake and cancer risk is complex and influenced by factors such as diet, lifestyle, genetic predisposition, and environmental exposures. While a diet rich in fruits, vegetables, and whole grains — natural sources of vitamins — is widely recommended for cancer prevention, the benefits and risks of vitamin supplementation for cancer prevention and treatment need careful evaluation through ongoing research. It underscores the importance of personalized nutrition advice from healthcare providers, especially for individuals at higher risk of cancer.
INFECTIOUS DISEASES AND CANCER
The relationship between infectious diseases and cancer is a significant area of study, with a notable proportion of cancers worldwide being linked to infectious agents such as viruses, bacteria, and parasites. These pathogens can contribute to cancer development through various mechanisms, including chronic inflammation, immune suppression, and the direct transformation of cells. On the flip side, the role of antibodies, which are produced by the immune system in response to infections, can be complex in the context of cancer. They can both help protect against cancer development by neutralizing infectious agents and, under certain circumstances, potentially contribute to autoimmunity that might inadvertently support cancer development.
Several infectious agents are recognized as carcinogens, with the World Health Organization estimating that about 15% of cancers worldwide are infection related.
Human Papillomavirus (HPV) is linked to almost all cervical cancers, as well as a significant proportion of anal, oropharyngeal, penile, vulvar, and vaginal cancers. HPV viruses can integrate their DNA into the host cell’s genome, leading to the overexpression of oncogenes like E6 and E7, which inactivate tumour suppressor proteins, driving cell transformation and cancer development.
Hepatitis B and C Viruses (HBV and HCV) are major causes of liver cancer (hepatocellular carcinoma). They can induce cancer through direct viral effects on cell signalling pathways and by promoting chronic inflammation and cirrhosis, which predispose to malignant transformation.
Helicobacter pylori is associated with stomach cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic infection leads to gastric inflammation and increases the risk of developing gastric ulcers, which can progress to cancer.
Epstein-Barr Virus (EBV) is linked to several types of cancer, including Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. The virus can immortalize B cells, leading to uncontrolled proliferation.
Antibodies, or immunoglobulins, are proteins produced by the immune system to identify and neutralize pathogens like bacteria and viruses.
Antibodies can help prevent cancers associated with infectious agents by neutralizing viruses and bacteria, thus preventing their oncogenic effects. Vaccines that stimulate antibody production against specific pathogens, like HPV and HBV vaccines, have been successful in reducing the incidence of associated cancers.
In cancer treatment, monoclonal antibodies are engineered to target specific antigens on cancer cells or to modulate the immune system’s response to cancer. Examples include trastuzumab (Herceptin), which targets the HER2 receptor in breast cancer, and pembrolizumab (Keytruda), which targets the PD-1 pathway to enhance the immune response against various cancers.
Some antibodies may have a role in promoting cancer. Autoantibodies against normal cellular proteins can contribute to chronic inflammation or immune dysregulation, both of which can promote cancer development. Additionally, the presence of certain autoantibodies can serve as biomarkers for the early detection of some cancers.
The intersection of infectious diseases, antibodies, and cancer is a complex and active area of research. Understanding how infectious agents contribute to cancer development has led to preventive measures like vaccines and treatments that significantly reduce the incidence of certain cancers. Meanwhile, leveraging the immune system’s ability to produce antibodies has opened new avenues in cancer treatment through immunotherapy. Continued research in these areas holds the promise of further breakthroughs in cancer prevention, diagnosis, and therapy.
LIFESTYLE, FOOD HABITS AND ENVIRONMENTAL FACTORS
Lifestyle, food habits, and environmental factors play critical roles in the incidence, development, and progression of cancer. These elements can either contribute to or protect against the risk of cancer through various mechanisms. Understanding the impact of these factors is crucial for developing effective cancer prevention strategies. Smoking and other forms of tobacco use are the single largest preventable cause of cancer worldwide, linked to lung, mouth, throat, pancreas, bladder, stomach, liver, colon, and cervix cancers. Excessive alcohol intake is associated with an increased risk of cancers of the mouth, throat, oesophagus, liver, breast, colon, and rectum. The risk is amplified when combined with tobacco use. Being overweight or obese increases the risk of several cancers, including breast, colon, endometrium, kidney, and oesophagus cancer. Regular physical activity is associated with a reduced risk of certain cancers. Excessive exposure to ultraviolet (UV) rays from the sun or tanning beds significantly increases the risk of skin cancers, including melanoma.
Diets high in fruits and vegetables are associated with a reduced risk of several types of cancer, possibly due to the protective effects of phytochemicals and antioxidants. Conversely, diets high in red and processed meats are linked to an increased risk of colorectal and possibly other cancers. Diets that contribute to weight gain and metabolic syndrome (characterized by high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels) can increase cancer risk. Obesity is a significant risk factor for several types of cancer. As mentioned, alcohol consumption is a risk factor for various cancers. The risk increases with the amount of alcohol consumed over time.
Exposure to carcinogens in the environment, such as asbestos, benzene, formaldehyde, and certain chemicals used in industry, can increase cancer risk. Long-term exposure to air pollution, particularly fine particulate matter, has been linked to an increased risk of lung cancer and possibly bladder cancer. Exposure to high levels of radiation, including radon gas, X-rays, gamma rays, and other forms of ionizing radiation, increases the risk of developing cancer.
The interplay between lifestyle, food habits, and environmental factors significantly influences cancer risk. The good news is that many cancer risks can be reduced by making healthy lifestyle choices, such as avoiding tobacco, limiting alcohol consumption, maintaining a healthy weight through diet and exercise, protecting skin from excessive UV exposure, and reducing exposure to known environmental carcinogens. Public health strategies aimed at promoting these behaviours, along with vaccination and other preventive measures against infections known to cause cancer, are crucial in the global effort to reduce the burden of cancer.
TOBACCO SMOKING
The molecular mechanisms by which tobacco smoke causes cancer are complex and multifaceted, involving a combination of chemical exposure, DNA damage, and disruptions to cellular processes. Many chemicals in tobacco smoke, such as polycyclic aromatic hydrocarbons (PAHs), benzene, and nitrosamines, can directly damage DNA by forming DNA adducts. A DNA adduct occurs when a carcinogenic chemical binds directly to DNA, interfering with the DNA’s normal processes. This can lead to mutations during cell division if not repaired correctly. Tobacco smoke also increases the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells. These reactive molecules can damage DNA, proteins, and cell membranes, leading to mutations and cellular dysfunction.
Tobacco smoke contains a complex mixture of over 7,000 chemicals, many of which are toxic and can cause cancer. Polycyclic Aromatic Hydrocarbons (PAHs) are a group of chemicals that are formed during the incomplete burning of tobacco, wood, coal, oil, garbage, or other organic substances. Examples include benzo[a]pyrene and naphthalene. Nitrosamines, specifically, tobacco-specific nitrosamines (TSNAs) such as N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These compounds are among the most potent carcinogens found in tobacco smoke. Formaldehyde is a volatile organic compound that is not only a significant irritant but also a known carcinogen. It is used in many industries, but in the context of smoking, it forms as a result of tobacco combustion. Found in many industrial processes and as a pollutant in the air, benzene is also present in cigarette smoke. It is a well-established cause of cancer, particularly leukaemia. Acetaldehyde, another toxic chemical found in cigarette smoke, which has been shown to be carcinogenic to animals and possibly humans, especially in relation to cancers of the upper respiratory tract. Arsenic is a heavy metal that is highly toxic and carcinogenic. It’s used in some agricultural and industrial products, and trace amounts can be found in tobacco smoke. Cadmium is a heavy metal found in tobacco smoke that can accumulate in the body over time, leading to various health issues, including cancer. Chromium is a metal that can increase the risk of lung cancer. It is found in tobacco smoke in a form that is highly absorbable and therefore particularly harmful. Polonium-210 is a radioactive element found in small amounts in tobacco smoke. It contributes to the cancer-causing potential of smoking. 1,3-Butadiene is a chemical used in the manufacture of synthetic rubber and found in the smoke of tobacco, it is considered to be a carcinogenic compound. These and other chemicals in tobacco smoke can act independently or synergistically to cause mutations in DNA, leading to cancer. This is why smoking is a major risk factor for many types of cancer, including lung, throat, mouth, bladder, kidney, and pancreas cancer.
Smoking can induce chronic inflammation, which in itself can promote cancer. Inflammatory cells can release reactive species that cause DNA damage, and signalling molecules that can promote a tumour-promoting environment. Exposure to tobacco smoke can impair the cell’s natural DNA repair mechanisms. For instance, tobacco carcinogens have been shown to inhibit the function of proteins involved in the repair of DNA double-strand breaks, such as BRCA2. When DNA damage is not properly repaired, it can lead to mutations that increase the risk of cancer.
Tobacco smoke can cause changes in the epigenetic regulation of genes, including DNA methylation, histone modification, and microRNA expression. These changes can alter the expression of oncogenes and tumour suppressor genes, contributing to cancer development. Some chemicals in tobacco smoke can lead to the activation of oncogenes (genes that, when mutated or expressed at high levels, can lead to cancer) or the inactivation of tumour suppressor genes (genes that normally prevent cancer by repairing DNA damage or inducing apoptosis in cells that are damaged).
Tobacco smoke can promote the growth of new blood vessels (angiogenesis) that tumours need to grow beyond a small size. Components of tobacco smoke can suppress the immune system’s ability to detect and destroy cancer cells. Tobacco smoke can stimulate the proliferation of damaged cells and enhance their ability to invade surrounding tissues, two key characteristics of cancer cells. The carcinogenic effects of tobacco smoke result from a combination of direct damage to DNA, the induction of mutations, alterations in gene expression, and the promotion of cellular environments conducive to cancer development and progression. Understanding these mechanisms has been crucial in establishing tobacco control measures and developing targeted therapies for tobacco-related cancers.
NITROSAMINES
Nitrosamines are a group of carcinogens found in tobacco smoke, certain foods (especially processed and preserved meats), and some occupational environments. They are also formed endogenously in the human body from nitrites and secondary amines, which can come from certain foods, medications, or other sources. Nitrosamines play a significant role in the development of various cancers, especially in organs like the stomach, esophagus, and lungs. The molecular mechanisms by which nitrosamines cause cancer involve multiple steps, including metabolic activation, DNA damage, and the disruption of normal cellular processes. Here’s a closer look at these mechanisms:
Nitrosamines require metabolic activation to exert their carcinogenic effects. They are metabolized primarily in the liver by cytochrome P450 enzymes (CYPs), especially CYP2E1, to form reactive intermediates. These intermediates are highly reactive and capable of binding to DNA, proteins, and other cellular molecules, leading to various forms of damage. The reactive intermediates formed during nitrosamine metabolism can covalently bind to DNA, forming DNA adducts. These adducts can cause mutations by inducing mispairing during DNA replication if not repaired. For example, O^6-methylguanine, a common adduct formed from nitrosamine exposure, can pair with thymine instead of cytosine during DNA replication, leading to G:C to A:T transition mutations.
Nitrosamine metabolism can also produce free radicals and reactive oxygen species (ROS), leading to oxidative DNA damage. This damage can result in base modifications, strand breaks, and other mutations if not properly repaired.
The mutations resulting from nitrosamine-induced DNA damage can lead to the activation of oncogenes and the inactivation of tumour suppressor genes, promoting uncontrolled cell proliferation and cancer development.
Nitrosamines can cause epigenetic changes, including DNA methylation and histone modification, altering the expression of genes involved in cell cycle regulation, apoptosis, and DNA repair mechanisms. These changes can further contribute to carcinogenesis. Some nitrosamines can induce chronic inflammation, a known risk factor for cancer. Inflammatory cells can produce reactive species that cause additional DNA damage and promote a microenvironment conducive to cancer progression. The carcinogenic effects of nitrosamines are primarily attributed to their ability to form DNA adducts and induce mutations after metabolic activation. These effects, coupled with oxidative stress, epigenetic alterations, and the promotion of a pro-inflammatory environment, contribute to the initiation and progression of cancer. Understanding these mechanisms has been critical for assessing cancer risk associated with nitrosamine exposure and for developing strategies to mitigate these risks, including dietary recommendations and regulations limiting nitrosamine levels in foods and other products. N-Nitrosodimethylamine (NDMA) is perhaps the most well-known nitrosamine due to its presence in various food items and water supplies. NDMA is a potent carcinogen and has been the subject of health advisories and regulatory scrutiny. N-Nitrosodiethylamine (NDEA) is similar to NDMA but with ethyl groups replacing the methyl groups. NDEA is also known for its carcinogenic properties and can be found in tobacco smoke, cosmetics, and as a contaminant in certain pharmaceuticals. N-Nitrosopyrrolidine (NPYR) is found in cooked meats, especially those that have been cured with nitrite preservatives. NPYR formation can also occur in the stomach from the reaction of dietary nitrites and secondary amines. N-Nitrosomorpholine (NMOR) is found in various food items and alcoholic beverages. It can be formed during the manufacturing process or when foods are cooked at high temperatures. N-Nitrosodi-n-butylamine (NDBA) is less common but can be found in certain industrial settings and in tobacco smoke. Like other nitrosamines, it is considered to have carcinogenic potential. N-Nitrosopiperidine (NPIP) occurs in certain food items, especially those containing pepper or cured meats. It’s another example of nitrosamines that can form through cooking or preserving processes involving nitrites.
Occupational exposure to certain hazardous substances has been recognized as a significant risk factor for the development of various types of cancer. Workers in specific industries may be exposed to carcinogens through inhalation, skin contact, or ingestion. The International Agency for Research on Cancer (IARC) and the National Institute for Occupational Safety and Health (NIOSH) provide guidelines and classifications for carcinogens, including those encountered in occupational settings.
Asbestos: Construction, shipbuilding, automotive (brake repair), insulation. Lung cancer, mesothelioma (a cancer of the lining of the chest and the abdominal cavity), and, less commonly, cancers of the larynx and ovary.
Benzene: Petrochemical, rubber industry, shoe manufacturing, gasoline-related industries. Leukemia (particularly acute myeloid leukemia – AML), non-Hodgkin lymphoma.
Formaldehyde: Manufacturing of resins and plastics, embalming in mortuaries, medical laboratories. Nasopharyngeal cancer, leukemia.
Arsenic: Mining, smelting, wood preservation, semiconductor manufacturing. Skin cancer, lung cancer, bladder cancer, and possibly kidney and liver cancers.
Chromium (VI) : Stainless steel welding, chrome plating, pigment production. Lung cancer and possibly nasal and sinus cancers.
Nickel : Nickel refining, stainless steel welding, manufacture of batteries. Lung cancer, nasal and sinus cancers.
Radon: Uranium mining, other underground mining operations.Lung cancer.
Silica Dust: Construction, mining, stone cutting, foundry work. Lung cancer, particularly in the presence of silicosis, a lung disease caused by inhaling silica dust.
Polycyclic Aromatic Hydrocarbons (PAHs): Coal tar production, paving and roofing with coal-tar pitch, aluminum production. Skin, lung, bladder, and gastrointestinal cancers.
Vinyl Chloride: PVC manufacturing, rubber industry. Angiosarcoma of the liver (a rare cancer of the blood vessels in the liver), lung cancer, liver cancer.
Shift Work: Healthcare, law enforcement, transportation, and others involving night or rotating shifts. Breast cancer, potentially due to disruptions in circadian rhythms and decreased melatonin production.
Potentized forms of implicated chemical substances in 30 c potency could be effectively incorporated in the MIT therapeutics of specific type of occupational cancer
Occupational cancer risks highlight the importance of protective measures, regulations, and monitoring in the workplace to minimize exposure to known carcinogens. Employers and regulatory bodies play crucial roles in ensuring workplace safety by implementing effective risk management practices, providing adequate protective equipment, and adhering to exposure limits. Additionally, awareness and education about occupational cancer risks can empower workers to take an active role in their own protection.
MODERN DRUGS THAT MAY CAUSE CANCER
The potential carcinogenic effects of modern chemical drugs are a concern in pharmacology and medicine. While the benefits of these drugs often outweigh their risks, especially for serious conditions, some have been associated with an increased risk of cancer after long-term use or in certain patient populations. It’s important to note that the identification of a drug as a potential carcinogen is based on a thorough review of scientific evidence, including laboratory studies, animal studies, and human epidemiological studies. Immunosuppressive drugs such ad Azathioprine, cyclosporine, tacrolimus etc suppress the immune system to prevent organ rejection in transplant patients or to treat autoimmune diseases. However, a suppressed immune system can decrease the body’s ability to surveil and eliminate cancer cells, increasing the risk of cancers, particularly skin cancers and lymphomas.
Certain hormone replacement therapies (HRT), oral contraceptives, and selective oestrogen receptor modulators (SERMs) like tamoxifen. While these drugs are effective for their intended uses, such as menopausal symptom relief (HRT), breast cancer treatment (tamoxifen), or contraception (oral contraceptives), some studies have linked them to increased risks of specific cancers. For example, tamoxifen is associated with a higher risk of endometrial cancer, and some forms of HRT have been linked to increased breast cancer risk.
Alkylating agents (e.g., cyclophosphamide), topoisomerase inhibitors (e.g., etoposide), and certain platinum-based drugs (e.g., cisplatin). These drugs are used to kill cancer cells, but they can also affect normal cells, leading to secondary cancers. Alkylating agents, for instance, can cause mutations in DNA, potentially leading to leukaemia years after treatment. Cyclophosphamide is a potent chemotherapeutic agent and immunosuppressant used to treat various types of cancers and autoimmune diseases. It belongs to the alkylating agents class, which works by binding to DNA, leading to cross-linking of DNA strands and ultimately causing cell death. This mechanism is effective against rapidly dividing cancer cells but can also affect normal cells, contributing to the drug’s side effects. A significant concern with the use of cyclophosphamide is its association with an increased risk of developing secondary cancers. These are new primary cancers that occur in patients previously treated with chemotherapy or radiation for a different cancer. Cyclophosphamide is metabolized in the liver to form aldophosphamide, which is then converted into active and inactive metabolites, including acrolein. Acrolein is excreted in the urine and has a direct toxic effect on the bladder epithelium, which can lead to bladder toxicity and increase the risk of bladder cancer. Alkylating agents like cyclophosphamide have been associated with a risk of AML and MDS, a group of disorders caused by poorly formed or dysfunctional blood cells. These conditions can develop several years after treatment with cyclophosphamide, often following a cumulative dose threshold.
Some studies have suggested a link between long-term use of certain NSAIDs and an increased risk of kidney cancer, though the evidence is not consistent. While the exact mechanism is unclear and the evidence is mixed, the potential for increased cancer risk may be related to the effects of these drugs on kidney function and inflammation pathways.
Some research has explored potential links between certain antidiabetic medications and cancer risk, such as an increased risk of bladder cancer with pioglitazone (a thiazolidinedione). Pioglitazone is an oral diabetes medicine that belongs to the thiazolidinedione class of drugs, also known as glitazones. It is used primarily to control blood sugar levels in patients with type 2 diabetes mellitus (T2DM). Pioglitazone works by increasing the sensitivity of liver, fat, and muscle cells to insulin, which facilitates the uptake of glucose from the bloodstream, thereby lowering blood sugar levels. Pioglitazone acts as an agonist for the peroxisome proliferator-activated receptor gamma (PPAR-γ), a type of nuclear receptor found in key tissues for insulin action such as adipose tissue, skeletal muscle, and the liver. Some studies have suggested an increased risk of bladder cancer with long-term use of pioglitazone, leading to its restricted use in some countries or in patients with a history of bladder cancer.
An increased risk of pancreatic cancer was observed with incretin-based therapies. The mechanisms are not fully understood and may involve changes in insulin levels, cell growth, and apoptosis pathways. Incretins are hormones that play a critical role in regulating blood sugar levels by enhancing insulin secretion from the pancreas in response to eating. These hormones are part of an enteroinsular axis, where the gastrointestinal tract communicates with the pancreatic islet cells to regulate insulin secretion and, hence, blood glucose levels. The two most well-known incretins are Glucagon-Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP). Incretins stimulate the pancreas to secrete insulin in a glucose-dependent manner, meaning insulin is released when blood glucose levels are high. This helps lower blood glucose levels. They also inhibit the secretion of glucagon, a hormone that increases blood glucose levels, from the pancreas when glucose levels are high, contributing further to the reduction of blood glucose. Incretins slow down the rate at which the stomach empties its contents into the small intestine, leading to a more gradual absorption of glucose into the bloodstream. Particularly, GLP-1 has been found to decrease appetite and food intake, contributing to weight loss in some individuals. GLP-1 Receptor Agonists (e.g., exenatide, liraglutide) are synthetic forms of incretin that mimic the action of GLP-1, enhancing insulin secretion, inhibiting glucagon release, slowing gastric emptying, and reducing appetite. They are used in the treatment of T2DM and have the added benefit of promoting weight loss.
It’s important to emphasize that the potential cancer risk associated with any drug must be weighed against the benefits it provides in treating specific conditions. Regulatory agencies like the FDA and EMA continuously review the safety profiles of approved drugs, including their potential to increase cancer risk. For patients, the best approach is to discuss the benefits and risks of any medication with their healthcare provider, considering both the short-term and long-term implications of their treatment options.
MIT APPROACH TO THERAPEUTICS OF CANCERS
DRUG MOLECULES act as therapeutic agents due to their CHEMICAL properties. It is an allopathic action, same way as any allopathic or ayurvedic drug works. They can interact with biological molecules and produce short term or longterm harmful effects, exactly similar to allopathic drugs. Please keep this point in mind when you have a temptation to use mother tinctures, low potencies or biochemical salts which are MOLECULAR drugs.
On the other hand, MOLECULAR IMPRINTS contained in homeopathic drugs potentized above 12 or avogadro limit act as therapeutic agents by working as artificial ligand binds for pathogenic molecules due to their conformational properties by a biological mechanism that is truly homeopathic.
Understanding the fundamental difference between molecular imprinted drugs regarding their biological mechanism of actions, is very important.
MIT or Molecular Imprints Therapeutics refers to a scientific hypothesis that proposes a rational model for biological mechanism of homeopathic therapeutics. According to MIT hypothesis, potentization involves a process of ‘molecular imprinting’, where in the conformational details of individual drug molecules are ‘imprinted or engraved as hydrogen- bonded three-dimensional nano-cavities into a supra-molecular matrix of water and ethyl alcohol, through a process of molecular level ‘host-guest’ interactions. These ‘molecular imprints’ are the active principles of post-avogadro dilutions used as homeopathic drugs. Due to ‘conformational affinity’, molecular imprints can act as ‘artificial key holes or ligand binds’ for the specific drug molecules used for imprinting, and for all pathogenic molecules having functional groups ‘similar’ to those drug molecules. When used as therapeutic agents, molecular imprints selectively bind to the pathogenic molecules having conformational affinity and deactivate them, thereby relieving the biological molecules from the inhibitions or blocks caused by pathogenic molecules.
According to MIT hypothesis, this is the biological mechanism of high dilution therapeutics involved in homeopathic cure. According to MIT hypothesis, ‘Similia Similibus Curentur’ means, diseases expressed through a particular group of symptoms could be cured by ‘molecular imprints’ forms of drug substances, which in ‘molecular’ or crude forms could produce ‘similar’ groups of symptoms in healthy individuals. ‘Similarity’ of drug symptoms and diseases indicates ‘similarity’ of pathological molecular inhibitions caused by drug molecules and pathogenic molecules, which in turn indicates conformational ‘similarity’ of functional groups of drug molecules and pathogenic molecules. Since molecular imprints of ‘similar’ molecules can bind to ‘similar ligand molecules by conformational affinity, they can act as the therapeutics agents when applied as indicated by ‘similarity of symptoms. Nobody in the whole history could so far propose a hypothesis about homeopathy as scientific, rational and perfect as MIT explaining the molecular process involved in potentization, and the biological mechanism involved in ‘similia similibus- curentur, in a way fitting well to modern scientific knowledge system.
If symptoms expressed in a particular disease condition as well as symptoms produced in a healthy individual by a particular drug substance were similar, it means the disease-causing molecules and the drug molecules could bind to same biological targets and produce similar molecular errors, which in turn means both of them have similar functional groups or molecular conformations. This phenomenon of competitive relationship between similar chemical molecules in binding to similar biological targets scientifically explains the fundamental homeopathic principle Similia Similibus Curentur.
Practically, MIT or Molecular Imprints Therapeutics is all about identifying the specific target-ligand ‘key-lock’ mechanism involved in the molecular pathology of the particular disease, procuring the samples of concerned ligand molecules or molecules that can mimic as the ligands by conformational similarity, preparing their molecular imprints through a process of homeopathic potentization upto 30c potency, and using that preparation as therapeutic agent.
Since individual molecular imprints contained in drugs potentized above avogadro limit cannot interact each other or interfere in the normal interactions between biological molecules and their natural ligands, and since they can act only as artificial binding sites for specific pathogenic molecules having conformational affinity, there cannot by any adverse effects or reduction in medicinal effects even if we mix two or more potentized drugs together, or prescribe them simultaneously- they will work.
Based on the detailed analysis of pathophysiology, enzyme kinetics and hormonal interactions involved, MIT approach suggests following molecular imprinted drugs to be included in the therapeutics of CANCERS:
Diethylstilbesterol 30, Progesterone 30, Dihydrotestosterone 30, Insulin 30, Luteinizing hormone 30, FSH 30, Telomer 30, Arsenic Alb 30, Cadmium 30, Chromium 30, Plumbum met 30, Ferrum met 30, Lactic acid 30, Hydrogen peroxide 30, Human papilloma virus 30, Histone 30, Hepatitis B virus 30, Helicobacter pylori 30, Epstein-Barr Virus 30, Tobacco smoke 30, Benzene 30, Naphthalene 30, N-nitrosonornicotine 30, Acetaldehyde 30, Nitrodimethyamine 30, Tamoxifen 30, Liraglutide 30, Pioglitazone 30, Platina 30, Acrolein 30, Cyclophosphamide 30.
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