tumorigenesis

Tumorigenesis, or oncogenesis, is the process by which normal cells transform into malignant neoplasms. It involves genetic and epigenetic alterations that accumulate over time and through clonal evolution, allowing cells to acquire growth advantages. The development of tumors is often described in stages: initiation, promotion, and progression. Initiation refers to the occurrence of heritable genetic or epigenetic alterations in a cell, typically DNA mutations or epigenetic marks that prime the cell for malignant growth. Promotion is the clonal expansion of initiated cells under selective pressures such as hormonal signals, inflammation, or exposure to promoters. Progression involves additional genetic changes that enable hallmark cancer traits: sustained proliferative signaling, resistance to cell death, evasion of growth suppressors, angiogenesis, invasion, and metastasis.

Molecular themes common to tumorigenesis include activation of oncogenes, inactivation of tumor suppressor genes, and defects in DNA damage response and genome maintenance leading to genomic instability. Key signaling pathways frequently disrupted include PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, and WNT/β-catenin. The tumor microenvironment—fibroblasts, immune cells, extracellular matrix, and inflammatory mediators—can promote growth and enable dissemination. Additional factors such as aging, persistent inflammation, and environmental exposures (carcinogens, ionizing radiation) modulate risk and timing. Metastasis involves epithelial-mesenchymal transition, degradation of the extracellular matrix, intravasation, survival in circulation, and colonization of distant sites. Understanding tumorigenesis underpins strategies for prevention, early detection, and targeted therapy, including mutation-informed drugs, anti-angiogenic agents, and immunotherapies.