Key Hallmarks of Cancer
The hallmarks of cancer represent acquired functional capabilities that enable neoplastic transformation and tumour progression.
Hanahan and Weinberg originally defined six hallmarks in 2000 and later expanded the framework.
Cancer cells sustain proliferative signalling.
They activate oncogenic pathways or overexpress growth factor receptors such as EGFR and HER2.
This drives continuous cell-cycle progression independent of external mitogens.
Cancer cells evade growth suppressors.
They inactivate tumour-suppressor genes, including TP53 and RB1, through mutation or deletion.
Loss of these checkpoints removes restraints on G1/S transition.
Cancer cells resist cell death.
They upregulate anti-apoptotic proteins such as BCL-2 and downregulate pro-apoptotic effectors.
Consequently, they survive DNA damage and oncogenic stress that would trigger apoptosis in normal cells.
Cancer cells enable replicative immortality.
They reactivate telomerase (TERT) or activate the alternative lengthening of telomeres (ALT) pathway.
This maintains telomere length and bypasses replicative senescence.
Cancer cells induce angiogenesis.
They secrete pro-angiogenic factors, notably VEGF-A, that activate endothelial cells.
New vessels form to meet the metabolic demands of the expanding tumour mass.
Cancer cells activate invasion and metastasis.
They undergo epithelial-mesenchymal transition (EMT), degrade extracellular matrix via matrix metalloproteinases, and intravasate.
Circulating tumour cells then colonise distant organs.
Additional hallmarks include deregulated cellular energetics and avoidance of immune destruction.
Tumour cells reprogramme metabolism toward aerobic glycolysis (Warburg effect) and express immune-checkpoint ligands such as PD-L1.
Enabling characteristics further support malignancy.
These include genomic instability, tumour-promoting inflammation, and non-mutational epigenetic reprogramming.
Collectively, these hallmarks provide a mechanistic framework for understanding carcinogenesis and for developing targeted therapies.