KIT
KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a lethal sarcoma into a chronic disease.
KIT and PDGFRA mutations drive GIST; imatinib, sunitinib, regorafenib, ripretinib, and avapritinib (PDGFRA D842V) form the sequence. KIT is also a target in systemic mastocytosis.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a lethal sarcoma into a chronic disease.
- 1 · What it is
KIT mutation is the driver behind most gastrointestinal stromal tumours, and the reason imatinib turned a lethal sarcoma into a chronic disease.
- 2 · What goes wrong in cancer
Stem-cell factor receptor tyrosine kinase.
- 3 · How drugs use it
10 products aim at KIT: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
Stem-cell factor receptor tyrosine kinase.
- GIST
- Mastocytosis
- Melanoma (mucosal/acral, rare)
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | 75-80% | GIST KIT mutation | PDGFRA in ~10% | Wikipedia |
| Melanoma | 2-3% | KIT mutation (acral/mucosal enriched) | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Avapritinib is the first drug for GIST driven by the PDGFRA D842V mutation, which resists every other kinase inhibitor; it is also approved for systemic mastocytosis.
The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.
An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.
The first drug to improve survival in FLT3-mutated AML, added to standard chemotherapy: median survival went from about two years to more than six.
Nilotinib is a second-generation CML pill that produces deeper responses faster than imatinib, at the cost of cardiovascular and metabolic side effects.
Pazopanib is the only multi-kinase inhibitor approved for soft-tissue sarcoma (excluding fat-derived tumours), used after chemotherapy fails.
Pexidartinib is the first drug for tenosynovial giant cell tumour, a benign but destructive joint tumour; it is effective but has liver toxicity that requires a restricted programme.
A sorafenib successor that became the first second-line drug proven to prolong life in liver cancer (2017).
A fourth-line GIST drug that locks KIT in an off state regardless of which resistance mutation the tumour has acquired.
Sunitinib is an anti-angiogenic pill approved for pancreatic neuroendocrine tumours, kidney cancer and GIST.
Latest papers
topQuery for this target: (TITLE:"KIT" OR ABSTRACT:"KIT") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about KIT, not a curated reading list.