01APC and colon cancer
APC controls the Wnt pathway. Normally APC is part of a destruction complex that degrades β-catenin. Without APC, β-catenin builds up, enters the nucleus and turns on growth genes like MYC and cyclin D1.
APC loss is often the first step in colorectal cancer, creating a small polyp. Additional mutations (KRAS, then TP53) turn it into carcinoma — the classic Vogelstein model of stepwise progression. Inherited APC mutation causes familial adenomatous polyposis, with hundreds of polyps by early adulthood.
02BRCA1/2 and DNA repair
BRCA1 and BRCA2 repair double-strand breaks by homologous recombination. Carriers of one mutant copy have a high lifetime risk of breast and ovarian cancer. Tumors that lose both copies must rely on error-prone repair, producing a distinctive mutation pattern.
That weakness is exploitable: PARP inhibitors (olaparib) block a backup repair route, and BRCA-deficient cells die — an idea called synthetic lethality.