Hallmarks of Malignancy: How Cancer Cells Behave

Malignancy defines the aggressive, autonomous behavior of cancer cells. Core hallmarks (Hanahan & Weinberg):

1. Uncontrolled proliferation: Autonomous growth signaling; evasion of growth suppressors (Rb, p53).
2. Invasion & destruction: Breach basement membrane; degrade ECM (MMPs); infiltrate locally.
3. Metastasis: Intravasation → circulation survival → extravasation → colonization at distant sites.
4. Angiogenesis: VEGF-driven neovascularization for nutrient supply.
5. Dedifferentiation: Loss of specialized function; stem-like plasticity.
6. Genomic instability: Mutations, CIN, chromothripsis; enables adaptation.
7. Apoptosis evasion: Bcl-2 overexpression, p53 loss, death receptor downregulation.
8. Immune evasion: PD-L1, MHC-I loss, T-cell exclusion.
9. Metabolic reprogramming: Warburg effect (aerobic glycolysis).

These traits collectively drive lethal progression. Targeting hallmarks underpins modern oncology (targeted therapy, immunotherapy).