Comprehensive Notes on Human Biology: Cancer Characteristics, Causes, and Treatments

Defining Cancer and Oncology

Cancer is defined as a disease characterized by the uncontrolled growth of cells. Although there are numerous distinct types of cancer and their underlying causes vary significantly, most cancers develop when a cell accumulates mutations that eventually lead to a loss of control over the cell cycle. Consequently, cancer is fundamentally understood as a cellular disease. Oncology is the formal medical name for the study of cancer.

Characteristics of Cancer Cells: Lack of Differentiation and Abnormal Nuclei

One of the primary characteristics of cancer cells is that they lack differentiation. Differentiation is the process of cellular development by which a cell acquires a specific structure and function. Cancer cells are nonspecialized and do not contribute to the functioning of any specific body part. Unlike specialized epithelial, muscle, nervous, or connective tissue cells, cancer cells look distinctly abnormal and fail to perform regular physiological tasks.

Furthermore, cancer cells possess abnormal nuclei. The nuclei in these cells are often enlarged and may contain an abnormal number of chromosomes. In addition to these nuclear irregularities, cancer cells frequently exhibit chromosomal mutations. While normal cells with damaged DNA typically undergo apoptosis (programmed cell death), cancer cells do not undergo this process, allowing them to survive despite their genomic instability.

Characteristics of Cancer Cells: Replicative Potential and Tumor Formation

Unlike ordinary somatic cells, which typically divide up to $60$ times before they stop dividing and potentially undergo apoptosis, cancer cells possess an unlimited potential to replicate. They are effectively immortal and continue to divide indefinitely. This immortality is facilitated by the fact that telomeres, the protective caps on the ends of chromosomes, remain at a constant length in cancerous cells. This occurs because the gene encoding the enzyme telomerase is continuously activated in cancer cells, enabling the enzyme to rebuild telomeres with each successive cell division.

Cancer cells also differ from normal cells in their physical growth patterns by forming tumors. Normal cells exhibit a phenomenon known as contact inhibition, which means they stop dividing when they come into contact with neighboring cells. Cancer cells have lost all such restraint; they pile on top of one another and grow in multiple layers, resulting in the formation of a tumor. As cancer develops, the most aggressive cells within the population become the dominant cells of the tumor mass.

Growth Factor Independence and Carcinogenesis

Normal cellular division is regulated by chemical signals called growth factors, which are categorized as either stimulatory or inhibitory. Cancer cells disregard these growth factors, continuing to divide even when stimulatory signals are absent and failing to respond to inhibitory growth factors that would normally halt proliferation. The development of cancer, known as carcinogenesis, is a gradual process that occurs in three primary steps: initiation, promotion, and progression.

During Initiation, a single cell undergoes a mutation that causes it to begin dividing repeatedly. This is followed by Promotion, where a tumor develops and the tumor cells continue to divide, undergoing further mutations in the process. Finally, Progression occurs when one cell undergoes a mutation that provides it with a selective advantage over other cells. This step is repeated several times until a cell eventually develops the ability to invade surrounding tissues.

Angiogenesis and Metastasis

For a tumor to grow larger than a billion cells, it must establish a well-developed capillary network to supply it with essential nutrients and oxygen. This process of forming new blood vessels is called angiogenesis. The low oxygen content often found in the center of a tumor may activate genes coding for angiogenic growth factors, which then diffuse into nearby tissues to trigger the formation of new vessels.

Cancer cells also exhibit the ability to undergo metastasis. Due to further mutations, cancer cells develop a disorganized internal cytoskeleton and become motile. These cells produce protease enzymes that degrade the basement membrane, allowing them to penetrate lymphatic or blood vessels. Metastasis is officially defined as the occurrence of new tumors at sites distant from the primary tumor.

Genetic Basis of Cancer: Proto-oncogenes and Tumor Suppressor Genes

Cancer results from gene mutations that disrupt the cell cycle, which consists of interphase followed by mitosis. The cycle is regulated by checkpoints where the cell monitors its condition and regulates division. Mutations in checkpoint proteins lead to a loss of control. There are two main classes of checkpoint proteins: proto-oncogenes and tumor suppressor genes. Proto-oncogenes code for proteins that promote the cell cycle and prevent apoptosis, while tumor suppressor genes code for proteins that inhibit the cell cycle and promote apoptosis.

When proto-oncogenes mutate, they become cancer-causing genes called oncogenes. These are gain-of-function mutations and are considered dominant, meaning they can cause cancer even if the mutation occurs in only one copy of the gene. For example, several proto-oncogenes code for Ras proteins that promote mitosis by activating cyclin, leading to uncontrolled division. Conversely, tumor suppressor genes can become inactive through loss-of-function mutations. These are recessive, requiring both copies of the gene to be mutated for the cell to lose control. A key example is $p53$, which normally activates DNA repair or promotes apoptosis. Many tumors lack $p53$ activity. Another example is the $BRCA1$ gene, which codes for a DNA repair enzyme; mutations in $BRCA1$ are linked to breast cancer because they allow cells with DNA damage to progress unchecked.

Classification of Cancers by Tissue Type

Cancer is classified based on the origin and the tissue affected. Carcinomas are cancers of the epithelial tissues and can affect the skin, breast, liver, pancreas, intestines, lung, prostate, and thyroid. Adenocarcinomas specifically affect glandular epithelial cells. Sarcomas arise in the muscles and connective tissues, such as bone and fibrous connective tissue. Leukemias are cancers of the blood, while Lymphomas are cancers of the lymphoid tissue. Blastomas are composed of immature cells where each cell resembles the cells of its original primary germ layer; for instance, a nephroblastoma contains cells similar to the mesoderm, from which the kidney develops. It is important to recall that embryos form from three primary germ layers: ectoderm, mesoderm, and endoderm.

Heredity and Environmental Carcinogens

Heredity plays a role in cancer predisposition. The first gene associated with breast cancer, discovered in $1990$, was named $BRCA1$, followed later by $BRCA2$. These are tumor suppressor genes following a recessive inheritance pattern. Since humans inherit two copies of every gene, if a mutated copy of $BRCA1$ or $BRCA2$ is inherited, a second mutation in the remaining healthy copy is required to increase the predisposition to cancer. This second mutation might lead to breast cancer if it occurs in the breast, or ovarian cancer if it occurs in an ovary.

Environmental factors also contribute through mutagens and carcinogens. A mutagen is any agent that causes mutations, while a carcinogen is a chemical that causes cancer by being mutagenic. Radiation is a major factor: ionizing radiation like X-rays can cause DNA mutations, and ultraviolet (UV) radiation from sunlight or tanning lamps is linked to skin cancer. X-rays constitute the majority of artificial radiation exposure; while benefits often outweigh risks, unnecessary procedures should be avoided and nearby tissues should be shielded.

Organic Chemicals, Viruses, and Dietary Choices

Organic chemicals found in tobacco smoke are known mutagens. Tobacco products or secondhand smoke are related to $80\%$ of all cancers, including those of the mouth, larynx, esophagus, pancreas, bladder, kidney, and cervix. The risk increases further when smoking is combined with alcohol consumption. Workplace pollutants such as asbestos, benzene, metals, dust, and pesticides also increase risk; for example, asbestos fibers increase the risk of lung cancer.

Certain viruses, known as oncoviruses, are linked to cancer. Hepatitis B and C viruses correlate with liver cancer, Human papillomaviruses (HPVs) are linked to cervical cancers, and the Epstein-Barr virus is associated with Burkitt lymphoma. Additionally, dietary choices such as a high-fat diet and obesity have been shown to parallel the incidence of breast and prostate cancers.

Early Detection and Warning Signs

Early detection significantly increases the likelihood of effective treatment. Future diagnostics focus on "fingerprints" or predictive biomarkers—molecular changes associated with cancer—using blood, saliva, or urine tests. One clinical tool for awareness is the CAUTION acronym for warning signs: C for Change in bowel or bladder habits; A for A sore that does not heal; U for Unusual bleeding or discharge; T for Thickening or lump in breast or elsewhere; I for Indigestion or difficulty in swallowing; O for Obvious change in wart or mole; and N for Nagging cough or hoarseness.

Routine screening and self-examinations are vital. The ABCDE rule helps examine skin for melanoma, the most serious skin cancer. Monthly self-exams can detect breast or testicular cancer. The Pap test is a crucial screening for cervical cancer where a physician samples cells for microscopic examination. Regular Pap tests are credited with preventing over $90\%$ of deaths from cervical cancer. Notably, women who receive the HPV vaccine still require regular Pap tests because the vaccine does not protect against all HPV types or existing infections.

Diagnostic Imaging and Procedures

Various imaging techniques are used to diagnose cancer. In breast cancer, a mammogram (X-ray) is used, while a colonoscopy is used for colon cancer to detect polyps. Ultrasound uses high-frequency sound waves to reveal the size and location of masses in the stomach, prostate, pancreas, kidney, uterus, and ovary. CT Scans (Computerized Tomography) use computer analysis of X-rays to create cross-sectional pictures. MRI (Magnetic Resonance Imaging) uses strong magnetic fields and radio waves, which is particularly useful for soft-tissue tumors or those surrounded by bone, such as in the brain or spinal cord.

PET Scans (Positron Emission Tomography) measure metabolic activity using a radioactive tracer. Because cancer cells have high glucose metabolism, a radioactive sugar called fluorodeoxyglucose (FDG) is used; it accumulates in malignant cells, highlighting them on the scan. A definitive diagnosis is often confirmed through a biopsy, which involves using a needle to remove a small sample of cells for examination.

Tumor Markers and Genetic Testing

Tumor marker tests are blood tests that look for antigens or antibodies produced in response to a tumor. For example, the carcinoembryonic antigen (CEA) can detect relapses in colon cancer. Other markers include PSA for prostate cancer, CA-125 for ovarian cancer, and AFP for liver tumors. Genetic testing is another tool, as hereditary cancers account for $5-10\%$ of all cases. Genetic testing identifies individuals at high risk based on family history, enabling targeted prevention. Genetic counseling is essential both before and after testing, and results can inform treatment or facilitate cascade testing for family members.

Standard and Emerging Cancer Therapies

Standard therapies include surgery, which is effective for localized or in-situ tumors; radiation therapy, which uses ionizing radiation to disrupt the cell cycle by damaging DNA; and chemotherapy. Chemotherapy is a systemic treatment targeting cells throughout the body, often used for metastatic cancers. Drug classes in chemotherapy include alkylating agents (disrupt DNA replication), antimetabolites (block growth enzymes), antitumor antibiotics (inhibit DNA enzymes), and mitotic inhibitors (block cell division).

Emerging treatments include Immunotherapy, which boosts the immune system via engineered cells or monoclonal antibodies. Gene therapy, such as $p53$ therapy, uses engineered viruses like adenoviruses to restore tumor-suppressor function. Genome editing using CRISPR aims to correct mutations or silence oncogenes. In the first CRISPR cancer trial, T cells were modified to remove three specific genes: two that interfere with the NY-ESO-1 receptor and one that limits the cells' killing ability, thereby enhancing their ability to target and destroy cancer cells.