Oncogenes in Cancer: Function, Mutations & Targeted Therapy

The most commonly mutated oncogene in human cancer. G12C/G12D/G12V mutations lock it in the GTP-active state, driving continuous RAS/MAPK and PI3K/AKT signalling. Present in ~90% of pancreatic, ~40% of colorectal, and ~25% of lung adenocarcinomas.

Master transcription factor driving ribosome biogenesis, metabolic reprogramming, and cell cycle entry. Overexpressed or amplified in ~70% of cancers; MYC overexpression sensitises cells to apoptosis, requiring co-mutations in BCL2 or TP53 loss to survive.

Receptor tyrosine kinase activating RAS/MAPK and PI3K/AKT. Exon 19 deletions and L858R define an important molecular subgroup of NSCLC; treatment evidence and regulatory language depend on variant, stage, specimen and regimen.

Serine/threonine kinase in the RAS/MAPK pathway. V600E mutation causes constitutive kinase activity independent of upstream RAS; present in ~50% of melanomas, ~60% of papillary thyroid cancers; targeted by dabrafenib/trametinib combination.

Receptor tyrosine kinase amplified in ~20% of breast cancers and ~10% of gastric cancers. Amplification leads to constitutive homodimerisation and downstream PI3K/MAPK signalling; targeted by trastuzumab, pertuzumab, and trastuzumab deruxtecan.

Catalytic subunit of PI3Kα; H1047R and E545K hotspot mutations constitutively generate PIP3, driving AKT/mTOR signalling. Found in ~30% of HR+ breast cancers; targeted by alpelisib, approved in PIK3CA-mutant breast cancer.

Cyclin-dependent kinase phosphorylating pRb at the G1/S restriction point. Amplified in ~15% of liposarcomas and glioblastomas; CDK4/6 inhibitors (palbociclib, ribociclib) are approved for HR+ breast cancer.

Serine/threonine kinase hub of the PI3K pathway promoting survival, protein synthesis, and cell cycle entry. E17K mutation in the pleckstrin homology domain causes constitutive activation; capivasertib approved for AKT1-altered HR+ breast cancer.

Transcription factor constitutively activated via JAK kinases, driving BCL-XL, MCL1, and cyclin D1 expression. Implicated in lymphoma, multiple myeloma, hepatocellular carcinoma, and NSCLC; JAK inhibitors suppress this axis.

Principal driver of tumour angiogenesis; transcriptionally activated by HIF-1α under hypoxia. Targeted by bevacizumab (anti-VEGFA antibody) and VEGFR TKIs including sunitinib and axitinib across multiple solid tumour types.