Oncogenes in Cancer: Function, Mutations & Targeted Therapy

Oncogenes are mutated or overexpressed forms of normal growth-promoting genes (proto-oncogenes) that provide cells with constitutive proliferative or survival signals. A single activating mutation in one allele is typically sufficient — dominant gain-of-function — in contrast to the biallelic inactivation required for tumor suppressors. Oncogenes are activated by point mutations (KRAS G12C), gene amplification (MYC, HER2), chromosomal translocations creating fusion proteins (BCR-ABL, EML4-ALK), or promoter mutations increasing expression.

Quick Answer

Gain-of-function mutations in growth-promoting genes that drive continuous cell division, even without normal growth signals. This category links the major genes to their molecular mechanisms, cancer associations, and related pathway pages.

Key Genes in This Category

KRAS

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.

MYC

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.

EGFR

Receptor tyrosine kinase activating RAS/MAPK and PI3K/AKT. Activating mutations in exons 19/21 drive ~15–50% of non-small-cell lung adenocarcinomas depending on ethnicity; targeted by osimertinib, the current first-line standard of care.

BRAF

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.

HER2

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.

PIK3CA

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.

CDK4

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.

AKT1

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.

STAT3

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.

VEGFA

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.

Explore Other Categories

Tumor Suppressor Genes

Proteins that act as molecular brakes on cell division. Loss of both copies unlocks uncontrolled proliferation.

Apoptosis Regulators

Genes that determine whether a damaged or stressed cell lives or dies. Cancer hijacks these to evade programmed cell death.

DNA Repair Genes

Genes maintaining genome integrity through detection and correction of DNA damage. Their loss drives mutagenesis and cancer predisposition.

Cell Cycle Regulators

Proteins controlling when and how cells divide. Disruption of these checkpoints is nearly universal in human cancer.

Gene descriptions are based on peer-reviewed literature from PubMed, UniProt, and NCBI Gene. Information is for educational purposes only.