Clinical meaning
Cancer results from uncontrolled cell proliferation caused by accumulated mutations in genes regulating cell growth, differentiation, and apoptosis. The cell cycle consists of G1 (growth and preparation for DNA synthesis), S phase (DNA replication), G2 (preparation for mitosis), and M phase (mitosis and cytokinesis). G0 is a quiescent resting state. Proto-oncogenes are normal genes that promote cell growth; when mutated (activated), they become oncogenes that drive uncontrolled proliferation (e.g., HER2/neu in breast cancer, RAS in pancreatic cancer, BCR-ABL in CML). Tumor suppressor genes normally inhibit cell growth and promote apoptosis; their inactivation removes growth brakes (e.g., p53 'guardian of the genome' mutated in >50% of cancers, BRCA1/2 in hereditary breast/ovarian cancer, Rb in retinoblastoma, APC in familial adenomatous polyposis). The metastatic cascade involves: local invasion (cancer cells produce matrix metalloproteinases that degrade basement membrane), intravasation (entering blood/lymphatic vessels), survival in circulation, extravasation (exiting at distant site), and colonization with angiogenesis (new blood vessel formation via VEGF). Tumor grading (I-IV) reflects cellular differentiation (how abnormal cells look microscopically). Tumor staging (TNM: Tumor size, Nodes, Metastasis) describes anatomic extent and is the most important prognostic factor. Tumor markers (PSA, CA-125, AFP, CEA, CA 19-9) are used for screening, monitoring treatment response, and detecting recurrence — NOT for definitive diagnosis.