Neoplastic Disease and Cancer Notes

What is Cancer?

• Cancer is a disease characterized by unregulated cell growth due to genetic mutations.

• It is not a single disease; rather, it encompasses a broad family of diseases that can manifest in any part of the body.

• Definition: A disease caused by uncontrolled division of abnormal cells.

• Typical prognosis without treatment is fatal due to:

  • Continuous cell proliferation disrupting normal cellular function.

  • Crowding out healthy cells.

• Statistics:

  • In 2018, there were 18 million diagnoses and 9.6 million deaths globally.

  • Up to 50% of the population may develop cancer at some point in life.

Hallmarks of Cancer

• Key characteristics shared by most cancers, originally summarised 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 (2011) to add:

  1. Deregulated metabolism.

  2. Evading the immune system.

Classification of Tumours

• Benign Tumours:

  • Small, slow-growing, non-invasive.

  • Well-differentiated and localized; cannot metastasize.

• Malignant Tumours:

  • Large, fast-growing, invasive, and poorly-differentiated.

  • Capable of metastasizing and infiltrating adjacent tissues.

Oncogenesis and Tumour Development

• Normal cell division is controlled by signals from growth factor receptors; they undergo apoptosis when signaling ceases or DNA is damaged.

• In cancer cells, mutations disrupt these controls, leading to uncontrolled growth:

  • They may proliferate without detecting neighboring cells.

  • They can produce their own growth signals and ignore apoptotic processes.

Growth of Cancer Cells

• A cancer cell might take about 2.5 years to grow into a detectable grape-sized tumor, dividing approximately every 2-6 weeks.

  • Tumor size indicators:

  • 1 million cells ≈ head of a pin.

  • 1 billion cells ≈ small grape.

Invasion and Metastasis

• Invasion: Cancer cells spread from the primary site, needing changes to a migratory phenotype and using enzymes to degrade the extracellular matrix (ECM).

• Metastasis: Tumor cells travel via the circulatory system to distant sites (commonly: bone, liver, brain, lungs, lymph nodes) forming secondary tumors.

  • Most cancer-related deaths are due to metastatic disease.

Tumor Angiogenesis & Necrosis

• Tumors need oxygen and nutrients; lack of these can create a necrotic core within larger tumors.

• Tumors secrete factors like VEGF to stimulate blood vessel growth (angiogenesis) towards them. This can be targeted with anti-angiogenic therapy.

Oncogenesis Process

• The transformation of normal cells into cancer cells involves multiple genetic changes and can encompass:

  • Changes in cell morphology and behavior

  • Developments like hyperplasia and dysplasia

  • Formation of localized tumors termed "carcinoma in situ" which may progress to malignancy.

Oncogenes and Tumor Suppressor Genes

• Oncogenes: Mutated forms of proto-oncogenes that promote cancer when activated (turned ON).

• Tumor Suppressor Genes: Normal genes that, when inactivated (turned OFF), can lead to cancer by failing to control cell division or repair DNA damage.

• Major genes include:

  • C-myc: transcription factor.

  • Ras: GTPase proteins.

  • P53: cell cycle regulator and apoptosis inducer.

  • BRCA1 & BRCA2: linked to breast and ovarian cancer.

Two-Hit Hypothesis

• Cancer may arise through two mutations:

  • Hereditary Tumors: One mutation inherited and one acquired.

  • Sporadic Tumors: Both mutations acquired.

Synergistic Mutations

• Simultaneous mutations in oncogenes (p53 and Ras) can exacerbate cancer development through collaborative gene expression.

Risk Factors for Cancer Development

• Lifestyle influences:

  • Smoking, obesity, poor diet, lack of exercise.

• Environmental exposure:

  • UV radiation, air pollution, industrial chemicals.

• Genetic predispositions related to family history.

Causes of Cancer

• Types:

  • Physical: Radiation exposure.

  • Chemical: Mutagens like benzopyrene or aflatoxins.

  • Biological: Viral and bacterial agents.

Biological Mutagens

• Viral: Can promote cancer via mechanisms such as degrading tumor suppressor genes or inducing chronic inflammation.

  • Notable viruses include HPV, HTLV, HBV, and Helicobacter pylori in stomach cancer.

Inheritance and Cancer Genetics

• Approximately 5-10% of cancers have hereditary components.

• Indicators of hereditary linkage include:

  • Rare cancers, early onset cancers, multiple cancer types in individuals, familial patterns.

  • Examples of genes involved: APC (colon), BRCA1/2 (breast), MET (renal).