Cancer Biology Basics

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Hallmarks of Cancer - Rebel Cell Rules

  • Sustaining proliferative signaling: Uncontrolled cell growth.
  • Evading growth suppressors: Ignoring "stop" signals (e.g., p53, RB loss).
  • Resisting cell death: Bypassing apoptosis.
  • Enabling replicative immortality: Unlimited cell divisions (telomerase).
  • Inducing angiogenesis: Forming new blood vessels (VEGF).
  • Activating invasion & metastasis: Spreading to distant sites.
  • Deregulating cellular energetics: Warburg effect (aerobic glycolysis).
  • Avoiding immune destruction: Hiding from immune system.
  • Genome instability & mutation: ↑ Genetic alterations.
  • Tumor-promoting inflammation: Inflammation aiding cancer. The Hallmarks of Cancer

⭐ Loss of function of the TP53 tumor suppressor gene is the most common genetic alteration in human cancers, occurring in >50% of cases.

Oncogenes & TSGs - Genes Gone Wild

  • Oncogenes: Arise from proto-oncogenes; drive cell growth (gain-of-function).
    • "Gas pedal" ➔ Uncontrolled proliferation.
    • Activation: Mutation, amplification, translocation.
    • Examples: RAS, MYC, HER2/neu (ERBB2), ABL, EGFR.
    • Dominant: Single allele mutation is sufficient.
  • Tumor Suppressor Genes (TSGs): Normally halt cell cycle, induce apoptosis, or repair DNA.
    • "Brake pedal" ➔ Failure to control growth.
    • Inactivation: Mutations, deletions, methylation (loss-of-function).
    • Knudson's "two-hit" hypothesis often applies.
    • Examples: p53, RB1 (retinoblastoma), BRCA1/2, APC, PTEN.
    • 📌 Oncogenes = On (accelerate); TSGs = Stop (brake).

p53, the "guardian of the genome," is mutated in over 50% of human cancers.

DNA Damage and Repair Pathways Leading to Cancer

Cell Cycle & Regulation - Cell Cycle Chaos

  • Phases: G1 (growth), S (DNA synthesis), G2 (mitotic prep), M (mitosis). (📌 Mnemonic: Go Sally Go Make)
  • Key Regulators:
    • Cyclins (D, E, A, B) activate CDKs (e.g., CDK4/6, CDK2, CDK1).
    • CDK Inhibitors (CKIs e.g., p16, p21, p27) halt progression.
  • Checkpoints (Fail-safes):
    • G1/S (Restriction Point): Governed by Rb, p53. Checks DNA integrity.
    • G2/M: Ensures DNA replication complete, damage repaired.
    • Spindle Assembly (M): Confirms correct chromosome attachment.
  • Cancer = Dysregulation:
    • Checkpoint failure (e.g., TP53, RB1 gene mutations) → uncontrolled proliferation.
    • Oncogenes (e.g., Cyclin D) overexpressed; Tumor Suppressor Genes lost.

TP53, the "guardian of the genome," is mutated in over 50% of human cancers, causing G1/S checkpoint failure & genomic instability.

Metastasis & Angiogenesis - The Great Escape

  • Metastasis: Cancer cells spread from primary to distant sites, forming secondary tumors.
    • Routes: Lymphatic (common for carcinomas), Hematogenous (common for sarcomas), Transcoelomic.
    • Common Sites: Lung, Liver, Bone, Brain (📌 LLBB: "Love Large Big Breakfast").
    • Mechanism: "Seed and Soil" (Paget) - tumor cells ("seed") require a favorable microenvironment ("soil").
  • Angiogenesis: Formation of new blood vessels; vital for tumor growth > 1-2 mm & metastasis.
    • "Angiogenic Switch": Balance shifts to favor pro-angiogenic factors.
    • Pro-angiogenic: VEGF, bFGF, PDGF.
    • Anti-angiogenic: Thrombospondin-1, Angiostatin.
    • 💡 Anti-VEGF therapy (e.g., Bevacizumab) is a key strategy.

    ⭐ VEGF is a primary driver of tumor angiogenesis.

Tumor Metastasis Cascade

High‑Yield Points - ⚡ Biggest Takeaways

  • Oncogenes (e.g., RAS, MYC) drive cancer by promoting uncontrolled cell growth.
  • Inactivation of tumor suppressor genes like p53 (genome guardian) and RB is critical for cancer development.
  • Metastasis, the spread to distant sites, is the main cause of cancer mortality.
  • Angiogenesis (new blood vessel formation, e.g., via VEGF) is essential for tumor growth.
  • Cancer arises from a multi-step accumulation of genetic/epigenetic changes.
  • Key hallmarks include evading apoptosis, limitless replication, and tissue invasion_._

Practice Questions: Cancer Biology Basics

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Cancer cells preferentially utilize glycolysis for energy production even in the presence of adequate oxygen. What is this phenomenon called?

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Flashcards: Cancer Biology Basics

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Treatment of desmoid tumor includes excision with wide margin clearance of _____cm to avoid recurrence.

TAP TO REVEAL ANSWER

Treatment of desmoid tumor includes excision with wide margin clearance of _____cm to avoid recurrence.

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