Cancerization

Cancerization is the process by which normal cells acquire the genetic and epigenetic changes that transform them toward a malignant phenotype. It is generally viewed as a multistep progression in which an initial genetic insult (a initiating mutation) is followed by clonal expansion, additional mutations, and epigenetic alterations that enable malignant traits. Over time these changes accumulate, giving rise to the hallmarks of cancer, such as sustained proliferative signaling, resistance to cell death, replicative immortality, angiogenesis, invasion, and genomic instability.

A related concept is field cancerization, where a wide area of tissue exposed to carcinogenic factors becomes populated by altered cells with pre-neoplastic changes. This can predispose to multiple independent tumors within the same region.

Common drivers include mutations in oncogenes and tumor suppressor genes, defective DNA repair, and epigenetic reprogramming. Carcinogenic exposures (tobacco smoke, ultraviolet light, environmental chemicals), inflammation, aging, and inherited susceptibility can influence the rate and pattern of cancerization.

Clinically, cancerization underscores the importance of early detection of dysplasia or carcinoma in situ, followed by surveillance or intervention before invasion of the basement membrane. Therapeutically, understanding cancerization supports strategies aimed at driver mutations, targeting the tumor microenvironment, and addressing intratumoral heterogeneity that can lead to treatment resistance. In summary, cancerization describes the progressive transformation of normal tissue into cancer through accumulating genetic and epigenetic alterations and clonal evolution.