PDGFRA
PDGFRA is a growth-factor receptor mutated in about 10% of GISTs, including the D842V mutation that resists imatinib but responds to avapritinib.
PDGFRA activating mutations (exons 12, 14, 18) define KIT-wild-type GIST with gastric location and epithelioid morphology; D842V (~60% of PDGFRA-mutant GIST) is imatinib-resistant but responds to avapritinib (~90% response, 2020). FIP1L1-PDGFRA fusions cause hypereosinophilic syndrome/chronic eosinophilic leukaemia that is exquisitely imatinib-sensitive; PDGFRA amplification occurs in glioblastoma (~15%) without a proven therapy. Olaratumab (anti-PDGFRα) failed in sarcoma (ANNOUNCE).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PDGFRA is a growth-factor receptor mutated in about 10% of GISTs, including the D842V mutation that resists imatinib but responds to avapritinib.
- 1 · What it is
PDGFRA is a growth-factor receptor mutated in about 10% of GISTs, including the D842V mutation that resists imatinib but responds to avapritinib.
- 2 · What goes wrong in cancer
Type III receptor tyrosine kinase (with KIT, CSF1R, FLT3); ligand PDGF-AA/BB dimerises the receptor, activating RAS/MAPK, PI3K and STAT pathways; D842V in the activation loop stabilises the active conformation.
- 3 · How drugs use it
No product in this corpus aims at PDGFRA yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
Type III receptor tyrosine kinase (with KIT, CSF1R, FLT3); ligand PDGF-AA/BB dimerises the receptor, activating RAS/MAPK, PI3K and STAT pathways; D842V in the activation loop stabilises the active conformation.
- GIST (~10%, gastric, KIT-wild-type)
- Chronic eosinophilic leukaemia (FIP1L1-PDGFRA)
- Glioblastoma (amplification ~15%)
- Dermatofibrosarcoma protuberans (COL1A1-PDGFB, ligand-driven)
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Glioma & glioblastoma | 15% | amplification | ||
| Gastrointestinal stromal tumour | 10% | PDGFRA mutation | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Latest papers
topQuery for this target: (TITLE:"PDGFRA" OR ABSTRACT:"PDGFRA") 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 PDGFRA, not a curated reading list.
Pages like this
not linked directly; found by shared links- ProductPexidartinib
Shares CSF1R, KIT, Sarcomas (soft tissue, bone, GIST), Small-molecule kinase inhibitors and the tag gap-fill.
- ProductLarotrectinib
Shares Receptor tyrosine kinase activation, Sarcomas (soft tissue, bone, GIST), Small-molecule kinase inhibitors and the tag gap-fill.
- ProductEntrectinib
Shares Receptor tyrosine kinase activation, Sarcomas (soft tissue, bone, GIST), Small-molecule kinase inhibitors and the tag gap-fill.
- ProductDuvelisib
Shares PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tag gap-fill.
- ProductUmbralisib
Shares PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tag gap-fill.
- ProductCopanlisib
Shares PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tag gap-fill.
- ProductTemsirolimus
Shares PI3K / AKT / mTOR, Small-molecule kinase inhibitors and the tag gap-fill.
- TargetMDM2
Shares Sarcomas (soft tissue, bone, GIST), Glioma & glioblastoma, Small-molecule kinase inhibitors and the tag gap-fill.