onkogenen

Oncogenes are genes that have the potential to cause cancer when mutated or overexpressed. In normal cells, related genes called proto-oncogenes regulate cell growth, differentiation, and division. An oncogene typically arises when a proto-oncogene is altered in a way that drives uncontrolled cell proliferation, often via constitutive activity or increased expression. Oncogenes can be inherited or acquired and are frequently found in many cancer types.

Activation mechanisms include point mutations that lock signaling proteins in an active state, gene amplification that increases gene dosage and protein levels, and chromosomal rearrangements that create fusion genes or place growth-promoting genes under strong regulatory elements. These alterations are usually dominant: a single mutated allele can promote transformation.

Common classes of oncogenes include growth factor receptors (such as the ERBB family), cytoplasmic signaling molecules (RAS family), and transcription factors (MYC family). Notable examples include KRAS, HRAS, BRAF; ERBB2/HER2; BCR-ABL; MYC; and PIK3CA as part of the PI3K pathway. The first oncogenes were discovered in retroviruses; the corresponding normal genes are called proto-oncogenes.

In cancer, oncogene activation contributes to malignant characteristics such as sustained proliferative signaling, evasion of growth suppressors, and resistance to cell death. Therapeutically, oncogenes can be targeted by drugs such as tyrosine kinase inhibitors (e.g., imatinib for BCR-ABL), EGFR inhibitors, and HER2-targeted therapies; resistance and tumor heterogeneity remain challenges.

See also: Proto-oncogene, Tumor suppressor gene, Oncogenic virus.