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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).
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.
PDGFRA is a growth-factor receptor mutated in about 10% of GISTs, including the D842V mutation that resists imatinib but responds to avapritinib.
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.
1 product aims at PDGFRA: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Tumour-specific alteration: 1 of 1 label readouts filed under it measure a sequence variant (PDGFRA exon 18 mutation (D842V)) absent from normal cells. HPA PDGFRA: RNA tissue enhanced (ovary 188 nTPM); high antibody staining in 5 normal tissues. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST), Brain and spinal cord tumours (all types)); approvals of single-target medicines aimed at it also list Myeloid neoplasms, Leukaemia, Skin cancer (all types), not counted; Open Targets associates it with 7 specific cancer types at or above 0.5 (gastrointestinal stromal tumor, acute myeloid leukemia, soft tissue sarcoma, renal cell carcinoma, non-small cell lung carcinoma, colorectal cancer and more). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: PDGFRA exon 18 mutation (D842V) label threshold; Human Protein Atlas PDGFRA tissue; Open Targets ENSG00000134853 associations
First described 1989. Earliest sequence paper UniProt cites for the protein: Claesson-Welsh et al, Proc. Natl. Acad. Sci. U.S.A, 1989, "cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
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.
RNA: tissue enhanced (ovary 188 nTPM), detected in all normal tissues.
Medium: Breast, Kidney, Ovary, Skin, Soft tissue.
RNA cancer enhanced: Glioblastoma Multiforme 101 pTPM.
No cancer stained high; medium in glioma, melanoma, ovarian cancer.
HPA PDGFRA tissue · HPA PDGFRA pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| 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.
Chiauranib is an experimental small-molecule drug from Chipscreen Biosciences in phase 3 trials for ovarian cancer, aimed at VEGF / VEGFR and KIT.
Query 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.
Shares PDGFRA exon 18 mutation (D842V), Avapritinib, KIT, Gastrointestinal stromal tumour (GIST).
Shares PDGFRA D842V-mutant GIST, Avapritinib, Gastrointestinal stromal tumour (GIST), Sarcomas (soft tissue, bone, GIST).
Shares GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria), Ripretinib, PDGFRA D842V-mutant GIST, KIT.
Shares GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria), Ripretinib, PDGFRA D842V-mutant GIST, KIT.
Shares GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria), KIT, Sunitinib, Gastrointestinal stromal tumour (GIST).
Shares PDGFRA D842V-mutant GIST, Avapritinib, Sarcomas (soft tissue, bone, GIST), Small-molecule kinase inhibitors.
Shares Ripretinib, Sunitinib, Gastrointestinal stromal tumour (GIST), Small-molecule kinase inhibitors.
Shares KIT, Gastrointestinal stromal tumour (GIST), Imatinib, Sarcomas (soft tissue, bone, GIST).