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A growth receptor amplified in squamous lung cancer and fused in a rare blood cancer. Pemigatinib is approved for the FGFR1-rearranged myeloid and lymphoid neoplasm, and pan-FGFR drugs block FGFR1 too, which is why they raise blood phosphate.
FGFR1 is amplified in a minority of squamous lung and breast cancers and rearranged, most often with ZMYM2 or BCR, in the myeloid or lymphoid neoplasm with eosinophilia and FGFR1 rearrangement, an aggressive disease that responds to pemigatinib, approved for it in 2022. The pan-FGFR inhibitors erdafitinib, pemigatinib and futibatinib all inhibit FGFR1, and because FGFR1 in the kidney controls phosphate excretion, hyperphosphataemia is their shared class effect and dose marker. FGFR1 amplification alone has proved a weak predictor of response to FGFR inhibitors in solid tumours.
In plain words · A growth receptor amplified in squamous lung cancer and fused in a rare blood cancer. Pemigatinib is approved for the FGFR1-rearranged myeloid and lymphoid neoplasm, and pan-FGFR drugs block FGFR1 too, which is why they raise blood phosphate.
A growth receptor amplified in squamous lung cancer and fused in a rare blood cancer. Pemigatinib is approved for the FGFR1-rearranged myeloid and lymphoid neoplasm, and pan-FGFR drugs block FGFR1 too, which is why they raise blood phosphate.
Receptor tyrosine kinase; gene amplification in squamous cancers and fusions in the 8p11 myeloproliferative syndrome; renal FGFR1 mediates the hyperphosphataemia of pan-FGFR inhibitors.
No product in this corpus aims at FGFR1 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 3 medicines aimed at it (Pemigatinib, Erdafitinib, Futibatinib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA FGFR1: RNA low tissue specificity; high antibody staining in 6 normal tissues; highest cancer staining head and neck cancer (2 of 4 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Myeloid neoplasms); approvals of single-target medicines aimed at it also list Biliary tract cancer (all types), Bladder & urothelial cancer, not counted; Open Targets associates it with 11 specific cancer types at or above 0.5 (encephalocraniocutaneous lipomatosis, renal cell carcinoma, urothelial carcinoma, pilocytic astrocytoma, colorectal cancer, non-small cell lung carcinoma and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas FGFR1 tissue; Open Targets ENSG00000077782 associations
First described 1988. Earliest sequence paper UniProt cites for the protein: Ruta et al, Oncogene, 1988, "A novel protein tyrosine kinase gene whose expression is modulated during endothelial cell differentiation". Source.
Receptor tyrosine kinase; gene amplification in squamous cancers and fusions in the 8p11 myeloproliferative syndrome; renal FGFR1 mediates the hyperphosphataemia of pan-FGFR inhibitors.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Bone marrow, Breast, Bronchus, Caudate, Cerebellum, Cervix.
Medium only: breast cancer, carcinoid, cervical cancer, colorectal cancer.
HPA FGFR1 tissue · HPA FGFR1 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 |
|---|---|---|---|---|
| Non-small-cell lung cancer | 17-22% | Focal high-level amplification | cBioPortal high-level amplification: 83 of 487, 17.0%, in lusc_tcga_pan_can_atlas_2018; 30 of 178, 16.9%, in lusc_tcga_pub; 102 of 1,144, 8.9%, in the combined nsclc_tcga_broad_2016; against 14 of 511, 2.7%, in lung adenocarcinoma. Amplification was found in a systematic copy-number search of 155 squamous cell lung cancers and confirmed by fluorescence in situ hybridisation in 22% of an independent squamous cohort (Weiss 2010). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | about 20% | FGFR1 amplification in squamous cell carcinoma of the lung | Weiss and colleagues found focal FGFR1 amplification in about a fifth of squamous lung cancers and rarely in adenocarcinoma. | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It shows that leaving androgen receptor dependence does not have to mean becoming neuroendocrine, and it names a treatable pathway for a group of men whose tumours would otherwise be described only by what they lack.
It explained why squamous lung cancer has no equivalent of an EGFR inhibitor: its commonest alterations are a transcription factor amplicon, a tumour suppressor deletion and an antioxidant switch, none of which is a drug target in the way a mutant kinase is.
It was the first therapeutically tractable alteration found in squamous lung cancer, and in the decade since it has become the standard example of amplification not equalling dependence, because copy number alone has selected patients poorly in trials.
Query for this target: (TITLE:"FGFR1" OR ABSTRACT:"FGFR1") 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 FGFR1, not a curated reading list.
Shares Erdafitinib, Futibatinib, Pemigatinib, FGF / FGFR signalling.
Shares Futibatinib, Pemigatinib.
Shares Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer, Non-small-cell lung cancer.
Shares Futibatinib, Pemigatinib.
Shares FGF / FGFR signalling, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Comprehensive genomic characterization of squamous cell lung cancers, Non-small-cell lung cancer.
Shares Futibatinib, Pemigatinib.
Shares Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer, Non-small-cell lung cancer.