Oncogenesis

Oncogenesis is the process by which normal cells acquire genetic and epigenetic alterations that transform them into malignant cells, forming tumors and potentially spreading to distant sites. It is driven by accumulated mutations in oncogenes and tumor suppressor genes, together with changes in gene regulation that disrupt normal cell growth and death controls.

Oncogenesis typically proceeds in stages — initiation, promotion, and progression — with clonal evolution at its core. Initiation involves genetic damage, promotion expands the altered clone, and progression includes further alterations that confer malignant traits such as invasion and metastasis.

Core mechanisms include the hallmarks of cancer: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Additional processes such as genomic instability, metabolic reprogramming, inflammation, and immune evasion support tumor development and adaptation.

Etiology is diverse, with environmental carcinogens, ionizing radiation, infections, and chronic inflammation contributing in many cancers, alongside inherited predispositions. Common driver mutations occur in genes such as TP53, KRAS, EGFR, BRCA1/2, and APC. Tumor heterogeneity arises from ongoing mutations across subclones, influencing behavior and treatment responses.

Knowledge of oncogenesis informs prevention, early detection, and therapy. Approaches include targeted therapies against specific mutations and immunotherapies, as well as strategies to reduce exposure to risk factors and monitor high-risk individuals.