Neoplastic transformation as a multi-step evolutionary process organized via the Hanahan-Weinberg hallmarks framework (2000/2011/2022): 8 classical capabilities, 2 enabling characteristics, 4 emerging dimensions, plus integrative…
Cancer Biology
Cancer biology
The study of neoplastic transformation as a multi-step, multi-scale, evolutionary process producing cell populations with progressively…
Hallmarks of cancer (2022 revision)
Hanahan 2022 expansion of the Hanahan-Weinberg 2000/2011 framework: eight classical hallmarks (sustained proliferative signaling; evading…
Hallmark: sustained proliferative signaling
Cancer cells acquire autonomy from homeostatic mitogen control. Mechanisms: autocrine production of growth factors (e.g. PDGF, TGF-α);…
Hallmark: evading growth suppressors
Cancer cells bypass cell-cycle checkpoints and anti-proliferative programmes enforced by tumor-suppressor proteins. Canonical failures: RB…
Hallmark: resisting cell death
Cancer cells evade apoptotic, necroptotic, and ferroptotic execution. Mechanisms: BCL2-family imbalance (BCL2/BCL-xL/MCL-1 overexpression…
Hallmark: enabling replicative immortality
Normal somatic cells undergo replicative senescence driven by telomere shortening after ~40-60 divisions (Hayflick limit). Cancer cells…
Hallmark: inducing angiogenesis
Tumors beyond ~1–2 mm diffusion-limited size induce neovascularization to supply oxygen and nutrients and remove waste. The angiogenic…
Hallmark: activating invasion and metastasis
Acquisition of migratory and tissue-remodeling capabilities. Steps: loss of E-cadherin (CDH1) releases epithelial adhesion; matrix…
Hallmark: deregulating cellular energetics
Cancer cells rewire metabolism to support rapid biosynthesis and redox homeostasis under variable oxygen. Canonical shift: aerobic…
Hallmark: avoiding immune destruction
Nascent tumors are edited by the immune system in three phases (elimination → equilibrium → escape) — Schreiber's cancer immunoediting.…
Enabling hallmark: genome instability and mutation
Elevated mutation rates and chromosomal instability (CIN) are enabling rather than definitional — they accelerate acquisition of the other…
Enabling hallmark: tumor-promoting inflammation
Chronic inflammation — whether infection-driven (H. pylori and gastric cancer; HPV and cervical cancer; HBV/HCV and hepatocellular…
Emerging hallmark: unlocking phenotypic plasticity
Hanahan 2022: malignant cells acquire the developmental plasticity normally locked away after terminal differentiation. Three modalities:…
Emerging hallmark: nonmutational epigenetic reprogramming
Hanahan 2022: heritable changes in tumor-cell state achieved through chromatin remodeling rather than DNA mutation. Evidenced by SWI/SNF…
Emerging hallmark: polymorphic microbiomes
Hanahan 2022: inter-individual variation in gut and tumor-associated microbiomes modulates cancer initiation, progression, and therapy…
Emerging hallmark: senescent cells
Hanahan 2022: senescence is no longer viewed as purely tumor-suppressive. Senescent cells in the tumor microenvironment — whether…
Tumor microenvironment
The heterotypic ecosystem surrounding cancer cells: cancer-associated fibroblasts (CAFs), endothelial cells, pericytes, infiltrating…
Cancer stem cells
A functionally defined subpopulation of tumor cells with self-renewal and tumor-initiating capacity — operationally measurable by…
Clonal evolution of cancer
Nowell 1976: tumors progress through repeated rounds of somatic mutation and clonal selection acting on heritable variation in malignant…
Two-hit hypothesis (Knudson)
Knudson 1971, from statistical analysis of retinoblastoma kinetics: tumor-suppressor genes require biallelic inactivation for phenotypic…
Metastatic cascade
The step-wise process by which a primary-tumor cell establishes a secondary tumor at a distant site: local invasion → intravasation into…
Epithelial-mesenchymal transition (EMT)
A conserved developmental programme reactivated pathologically in cancer and fibrosis. Cells lose apical-basal polarity and…
Tumor heterogeneity
Cancer populations exhibit genetic, epigenetic, transcriptional, and phenotypic diversity both within a single tumor (intratumoral) and…
Driver vs passenger mutations
A somatic mutation is a 'driver' if it confers a selective fitness advantage to the clone it arises in; 'passenger' otherwise. Most…
Synthetic lethality in cancer
Two gene perturbations are synthetically lethal if each alone is tolerated but their combination kills the cell. Exploited therapeutically…