Onkogenese

Onkogenese is the process by which normal cells acquire genetic and epigenetic changes that allow them to become cancer cells. It involves activation of oncogenes, inactivation of tumor suppressor genes, and alterations in genes that regulate genome stability, cell cycle control, and metabolism.

Proto-oncogenes can be converted to oncogenes by point mutations, gene amplification, or chromosomal translocations that create fusion proteins with abnormal activity. Loss or inactivation of tumor suppressor genes such as TP53 or RB removes restraints on growth, cell cycle progression, and DNA damage responses. Together, these changes disrupt normal cellular regulation and can promote malignant transformation.

Cancer development is typically a multistep process, with initiation, promotion, and progression, and is driven by accumulating driver mutations in clonal lineages. Clonal evolution and tumor heterogeneity arise as subclones acquire distinct alterations, shaping growth, invasion, and treatment response.

Common cancer hallmarks include sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis, and invasion/metastasis. Additional alterations, such as metabolic reprogramming and genomic instability, support these traits and enable adaptation to changing environments.

Environmental factors (carcinogens, ionizing radiation), infectious agents (oncogenic viruses), and inherited predispositions contribute to onkogenese. Understanding the process helps explain why cancers arise and progress, and informs prevention, early detection, and the development of targeted therapies that inhibit specific oncogenic pathways.