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FGFR2
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Interpretation 273
Tier 2
FGFR2
Variants
Primary Sites
Endometrium
Tumor Types
Adenocarcinoma
Interpretation

The receptor tyrosine kinase FGFR2 is one of four fibroblast growth factor receptors designated FGFR1-4 that activate FGF signalling upon trans-autophosphorylation of the receptor dimers. Some genetic alterations of FGFR2 lead to aberrant activation of FGFR2 signaling cascades due to the creation of autocrine signaling loop or the release of FGFR2 from autoinhibition. About 10-16% of primary endometrial cancers harbor activating mutations in FGFR2. These mutations are more frequent in cancers of endometrioid histological subtype compared with serous or clear-cell subtypes. Gain-of-function mutations in the kinase domain lead to ligand-independent activation of the receptor, whereas mutations in the extracellular ligand-binding domain increase the affinity for fibroblast growth factors (FGFs). Both types of mutations have been shown to be potentially oncogenic in endometrial cancer cell lines. In cell line and xenograft experiments, inhibition/knockdown of FGFR2 results in anti-tumour effects, suggesting the oncogenic role of FGFR2, raising the potential of FGFR2 as a target of therapy in FGFR2 driven cancers. Therefore, FGFR-pathway inhibition remains potentially promising in this patient population.

Citations
  1. Tabernero J, et al. Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol 2015;33(30):3401-8
  2. Block MS, et al. Second-line dovitinib in metastatic endometrial cancer. Lancet Oncol 2015;16(6):604-6
  3. Konecny GE, et al. Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study. Lancet Oncol 2015;16(6):686-94
  4. Powell MA, et al. A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study. Gynecol Oncol 2014;135(1):38-43
  5. Katoh M, et al. FGF receptors: cancer biology and therapeutics. Med Res Rev 2014;34(2):280-300
Last updated: 2016-06-01 13:38:33 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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