Introduction to Cancer Overview

Introduction to Cancer

• Cancer is a collection of diseases, not just one disease.
• It's characterized by uncontrolled cell growth and invasion.
• Affects virtually any organ or cell type.
• Has various causes.
• Outcomes range from treatable to untreatable.
• Different therapeutic approaches are employed.

Types of Cancer

• Cancer refers to hundreds of different diseases.
• There are over 200 types of cancer.
• Each case is unique because molecular and cellular events arise randomly.
• Classification usually based on the body part and cell type where the cancer originates.

Types of Cancer (Examples)

• Carcinoma: Most common; arises from epithelial tissue (e.g., breast, lung, liver).
• Sarcoma: Connective tissues (e.g., bones, muscles, blood vessels).
• Myeloma: Bone marrow (plasma cells).
• Leukemia: Bone marrow (white blood cells, erythrocytes).
• Lymphoma: Lymph nodes/glands (spleen, tonsils, thymus).
• -oma (e.g., Lipoma, adenoma): Benign tumours (not spreading).

Cancer Prefixes

• adeno-: gland
• chondro-: cartilage
• erythro-: red blood cell
• hemangio-: blood vessels
• hepato-: liver
• lipo-: fat
• lympho-: lymphocyte
• melano-: pigment cell
• myelo-: bone marrow
• myo-: muscle
• osteo-: bone

Cancer Type and Prognosis

• Survival rates vary greatly between cancer types.
• Specific types, such as non-melanoma skin and prostate cancer, generally have higher five-year survival rates.
• Cancers of the pancreas, esophagus, and lung tend to have lower survival rates.

Important Terminology

• Neoplasm: New disorganised growth or tumour with a net increase in dividing cells.
• Tumour: A mass of abnormal cells.
• Benign tumours: Enlarges but doesn't invade surrounding tissues and doesn't spread.
• Malignant tumours: Malignant tumours invade surrounding tissue and spread.
• Metastasis: Tumour spreading beyond the original site into other areas in the body.
• Carcinogenesis: The process of forming a cancer via carcinogens.

Properties of Cancer

• Cancer cells are formed when normal cells undergo specific changes allowing them to proliferate without normal limits and spread to surrounding tissues.
• Usually multiple changes are needed to turn a normal cell into a cancer cell.
• Inherited susceptibility and/or lifestyle influences cancer progression.

Tumorigenesis (Multi-step Process)

• Cancer development is a multi-step process.
• The process involves several stages through which benign tissues become cancerous.
• This progression involves pre-cancerous cellular changes, which are reversible.
• Carcinoma in situ (CIS), cervical intraepithelial neoplasia (CIN), ductal carcinoma in situ (DCIS), and prostatic intraepithelial neoplasia (PIN) are examples of precancerous conditions.

Normal Cell Proliferation

• Ongoing throughout life to allow development, repair, or regeneration of tissues.
• Cell division is tightly regulated at multiple levels.

Phases of the Cell Cycle

• M-phase: Mitosis and cytokinesis (prophase, metaphase, anaphase, telophase).
• GAP 2 (G2): RNA and protein synthesis required for M-phase.
• S-phase: DNA synthesis.
• GAP 1 (G1): RNA and protein synthesis required for S-phase.
• GAP 0 (G0): Quiescent (resting) cells.

Mitosis and Cytokinesis

• Prophase: Chromosomes condense; centrosomes assemble; nuclear membrane begins to break down.
• Metaphase: Chromosomes align and attach to spindle fibers.
• Anaphase: Sister chromatids pull apart and migrate to poles.
• Telophase: Chromatids de-condense; new nuclear membranes form.
• Cytokinesis: Nuclear membrane completely surrounds decondensed chromosomes; contractile ring pinches off cytoplasm of "mother" cell and daughter cells are formed.

Positive Regulators of the Cell Cycle

• Cyclin B, nuclear D1, cyclin E, cyclin A, CDCs play a role in regulating the cell cycle
• Program influenced by extracellular signals.
• Cell autonomous program.

Regulation of the Cell Cycle

• Activity of cyclin:CDK complexes is regulated at multiple levels.
• Expression of regulatory cyclin component of complex (e.g., E2F, pRb).
• Regulation of cyclin:CDK complex activity (phosphorylation/de-phosphorylation by CDC25 phosphatases).
• Direct inhibition of complex activity by cyclin-dependent kinase inhibitors (e.g., p27).

Cell Cycle Inhibitors

• p16INK4A, p15INK4B, p18INK4C, p19INK4D, p57Kip2, p27Kip1, p21 Cip1 play a role in inhibiting the cell cycle.

Cell Cycle Checkpoints

• G2 checkpoint: Before entry into M-phase to check if DNA replication is complete.
• DNA damage checkpoint: Halting replication if DNA is damaged.
• Spindle assembly checkpoint: Checking for proper assembly of mitotic spindle before anaphase.

Hallmarks of Cancer

• Sustained proliferative signaling: Cell loses requirement for growth factors to stimulate cell division (e.g., Ras, HER2).
• Evading growth suppressors: Loss of function of tumour suppressor, such as pRB, p53.
• Resisting cell death: Cancer cells gain ability to avoid apoptosis (e.g., pro-survival factors like IGF).
• Enabling replicative immortality: Tumour cells effectively immortal by rebuilding telomeres using telomerase.
• Inducing angiogenesis: Tumours stay small until they secure a blood supply.
• Activating invasion and metastasis: Cells start to break away from the main tumour, invade surrounding tissue and enter blood vessels.

DNA Mutations in Cancer Development

• DNA in cells is damaged around 10,000 times per day.
• Most of this damage is repaired.
• Mutations occur randomly throughout the genome, often in non-coding regions or within genes with no effect.
• Accumulated mutations can cause genome instability, increasing the likelihood of further mutations in cancer development.

Stages of Cancer and Survival

• Initiation: First mutations that prompt increased proliferation.
• Promotion: Additional mutations for further proliferation.
• Tumor progression: The tumour grows further.
• Stages of cancer (e.g., 1-4) are important for determining treatment and prognosis.
• TNM scheme (tumor, node, metastasis) gives additional details for grading.
• Survival rates vary considerably between cancer types and stages of diagnosis.

Leading Cancer Types

• Leading causes of cancer death or diagnosis as of 2019 were given.

How does cancer kill?

• Interferes with normal organ function (blockage, deprivation of nutrients, pressure).
• Interferes with metabolic processes (malnutrition, calcium changes, liver enzyme function, blood cell or hormone production).
• Causes muscle wasting.

Risk Factors for Cancer

• Age.
• Genetics.
• Smoking.
• Inactivity/lack of physical activity.
• Obesity.
• Alcohol.
• Diet (e.g., lack of fruit, vegetables, salt, processed foods, red meats).
• Infections (cause ~18% of cancers globally.)

Cancer Screening Programmes

• Early detection, diagnosis, and treatment improve patient outcomes.
• Self-checks can be useful for skin, breast, and testicular cancers.
• NHS screening programmes are available for bowel, cervical, and breast cancers.