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Neoplastic Disease and Cancer Review

Learning Outcomes

  • Oncogenesis and Tumours: Describe the process of oncogenesis and its association with tumour development.

  • Malignancy, Angiogenesis and Metastasis: Explain malignancy, angiogenesis, and metastasis processes.

  • Causes of Cancer: Identify and explain various causes of cancer: viral, genetic, mutagen, and physical.

  • Oncogenes and Tumour Suppressor Genes: Explain their roles in cancer. Discuss inheritance in cancer genetics.

What is Cancer?

  • Definition: Cancer is the unregulated growth of cells caused by genetic mutations.

  • Nature of Cancer: Not a single disease but an umbrella term for a large family of diseases affecting any part of the body.

  • Characteristics:

    • Uncontrolled division of abnormal cells.

    • Can cause death if untreated due to crowding out healthy cells.

    • In 2018, there were 18 million diagnoses and 9.6 million deaths; approx. 50% of the population will develop cancer.

    • Cancer cells have unlimited proliferation, invade tissues, and migrate to other body parts.

Hallmarks of Cancer

  • Key Characteristics (summarized by Hanahan and Weinberg):

    1. Self-sufficiency in growth signals.

    2. Insensitivity to anti-growth signals.

    3. Evading apoptosis.

    4. Limitless replicative potential.

    5. Sustained angiogenesis.

    6. Tissue invasion and metastasis.

  • Updated Hallmarks (2011):

    1. Deregulated metabolism.

    2. Evading the immune system.

Classification of Tumours

Benign Tumours:

  • Characteristics:

    • Small, slow-growing, non-invasive.

    • Well-differentiated and localized.

    • Cannot invade or metastasize.

Malignant Tumours:

  • Characteristics:

    • Large and fast-growing.

    • Invasive, poorly differentiated.

    • Can metastasize and destroy surrounding tissues.

Oncogenesis

  • Process: Normally, cell division is controlled by growth factor receptors and apoptosis signals. In cancer:

    • Mutations remove controls on growth.

    • Cancer cells may ignore neighbouring signals, produce growth hormones, and bypass apoptosis.

  • Tumour Development: Takes several years with multiple genetic changes leading to hyperplasia, dysplasia, or carcinoma in situ.

Growth of Cancer Cells

  • Cancer cells can divide every 2-6 weeks.

  • It may take 2.5 years for one cancer cell to develop into a grape-sized tumour.

  • Tumour size milestones:

    • 1 million cancer cells = head of a pin.

    • 1 billion cancer cells = small grape.

Invasion and Metastasis

Invasion:

  • Definition: Spread of cancer cells from primary site to other body parts.

  • Mechanism: Involves a change to a migratory phenotype and secretion of enzymes to degrade ECM.

Metastasis:

  • Tumour cells are transported through the circulatory system to specific locations (bones, liver, brain, lungs, lymph nodes).

  • Most cancer fatalities result from metastatic disease, which worsens prognosis.

Tumour Angiogenesis & Necrosis

  • Necrosis: As tumours expand, their centres may not receive enough nutrients.

  • Angiogenesis: Tumours secrete factors like VEGF to promote blood vessel growth for nutrient supply, which can be targeted by anti-angiogenic therapies.

Oncogenesis Mechanism

  • Terminology:

    • Tumourigenesis, carcinogenesis, or oncogenesis refers to the transformation of normal cells into cancer cells.

  • Multi-step Process: Changes in gene expression lead to cancer development, involving mutations in both tumour suppressor and oncogenes.

Oncogenes and Tumour Suppressor Genes

  • Oncogenes: Mutated proto-oncogenes that promote cancer.

  • Tumour Suppressor Genes: Regulate cell cycle, DNA repair, and apoptosis. Cancer arises when these genes are inactivated.

  • Key Genes:

    • Oncogenes: C-myc, Ras.

    • Tumour Suppressors: P53, BRCA1, BRCA2.

Two-Hit Hypothesis

  • Hereditary Tumour: One inherited mutation causes cancer; requires a second acquired hit to develop.

  • Sporadic Tumour: Two acquired mutations lead to cancer.

Synergistic Mutations

  • Concept: Mutations in genes like p53 and Ras can synergistically lead to uncontrolled cell growth by regulating similar gene sets.

Risk Factors for Cancer Development

  • Lifestyle: Smoking, unhealthy diet, lack of exercise, obesity, UV exposure.

  • Environmental: Air and industrial pollution, chemical exposures.

  • Genetic: Family history of cancer.

Causes of Cancer

  • Categorized as:

    • Viral: HPV (cervical), HIV (not directly cancerous but lowers immunity).

    • Genetic: Mutations in critical genes like APC for colorectal cancer.

    • Mutagen: Chemical exposure (e.g., benzopyrene).

    • Physical: Radiation.

Inheritance and Cancer Genetics

  • Hereditary Factors: Approximately 5-10% of cancers are due to inherited mutations.

  • Indicators of Hereditary Cancer:

    • Rare cancer types in families.

    • Earlier age diagnoses.

    • Multiple cancers in individuals.

  • Notable Genes: BRCA1 and BRCA2 increases breast and ovarian cancer risk (55-65% and 45%, respectively).

Recommended Reading

  • Crowley, Chapter 10 Neoplastic Disease

  • Chiras, Chapter 20