U01.04.023 Hallmarks of cancer

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Learning Objectives

Master the Hallmarks of Cancer, the fundamental biological capabilities acquired during the multistep development of human tumors. Understand the molecular mechanisms of Growth Signal Self-Sufficiency, Immune Evasion, and the metabolic shift known as the Warburg Effect.

1. Proliferation and Survival Signals

Cancer cells bypass normal homeostatic controls by acquiring mutations in proto-oncogenes and tumor suppressor genes, allowing for autonomous growth and resistance to programmed cell death.

Hallmark Molecular Mechanism Examples
Growth Self-Sufficiency Mutations in RAS, MYC, or HER2. Autocrine loops (↑ PDGF in brain tumors).
Anti-growth Insensitivity Loss of Rb or E-cadherin function. Loss of contact inhibition (NF2 mutations).
Evasion of Apoptosis Mutations in TP53 or BCL2. Follicular B-cell Lymphoma (t[14;18]).
Limitless Replication Reactivation of Telomerase. Prevents cell aging and chromosome shortening.

 

2. Metabolism and Angiogenesis

To sustain rapid division, tumors must alter their metabolism to prioritize biomass synthesis and secure a dedicated blood supply for nutrients and oxygen.

Hallmark Mechanism Outcome
Warburg Effect Shift to Aerobic Glycolysis. Provides carbon for synthesis; ↑ Lactic acid.
Sustained Angiogenesis Increased VEGF or decreased inhibitors. Leaky, dilated vessels (neoangiogenesis).

3. Immune Evasion and Invasion

Successful tumors must remain “invisible” to the immune system while gaining the ability to physically migrate through the extracellular matrix (ECM).

Process Key Mediators Escape Mechanism
Immune Evasion ↓ MHC Class I; ↑ PD-L1. Cytotoxic T-cells cannot recognize or kill tumor.
Tissue Invasion Metalloproteinases; Loss of E-cadherin. Degradation of basement membrane and ECM.
Metastasis Lymphatic/Hematogenous spread. “Homing” to specific organs (e.g., Lung to Adrenals).

 

Activity

High-Yield Mnemonics & Tips:

  • Warburg Paradox: Even with plenty of oxygen, cancer cells prefer glycolysis. It’s inefficient for energy (ATP) but highly efficient for building cell parts.
  • Invasion Sequence: Remember the steps: 1. Detach (Lose E-cadherin) → 2. Degrade (MMPs) → 3. Attach (Laminin/Fibronectin) → 4. Move (Locomotion).
  • Immune Checkpoints: This is the basis of modern immunotherapy. By blocking the molecules tumor cells use to hide (like PD-1/PD-L1), we “unmask” the tumor for the immune system.

Activity: