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|Ref Type||Journal Article|
|Authors||Perera TPS, Jovcheva E, Mevellec L, Vialard J, De Lange D, Verhulst T, Paulussen C, Van De Ven K, King P, Freyne E, Rees DC, Squires M, Saxty G, Page M, Murray CW, Gilissen R, Ward G, Thompson NT, Newell DR, Cheng N, Xie L, Yang J, Platero SJ, Karkera JD, Moy C, Angibaud P, Laquerre S, Lorenzi MV|
|Title||Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor.|
|Abstract Text||Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor (FGFR) family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases. JNJ-42756493 shows rapid uptake into the lysosomal compartment of cells in culture, which is associated with prolonged inhibition of FGFR signaling, possibly due to sustained release of the inhibitor. In xenografts from human tumor cell lines or patient-derived tumor tissue with activating FGFR alterations, JNJ-42756493 administration results in potent and dose-dependent antitumor activity accompanied by pharmacodynamic modulation of phospho-FGFR and phospho-ERK in tumors. The results of the current study provide a strong rationale for the clinical investigation of JNJ-42756493 in patients with tumors harboring FGFR pathway alterations. Mol Cancer Ther; 16(6); 1010-20. ©2017 AACR.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Erdafitinib||Balversa||JNJ-42756493||FGFR Inhibitor (Pan) 25||Balversa (erdafitinib) selectively inhibits FGFR1-4, resulting in decreased downstream signaling, and potentially leading to reduced growth of tumors with activated FGFR signaling (PMID: 28341788, PMID: 28965185). Balversa (erdafitinib) is FDA approved for use in patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 genetic alterations (FDA.gov).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|FGFR2 amp||colorectal cancer||sensitive||Erdafitinib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Balversa (erdafitinib) inhibited tumor growth in an FGFR2-amplified colorectal cancer cell line xenograft model (PMID: 28341788).||28341788|
|FGFR2 amp||stomach cancer||sensitive||Erdafitinib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Balversa (erdafitinib) inhibited proliferation of a gastric cancer cell line with FGFR2 amplification in culture, and inhibited tumor growth in xenograft models (PMID: 28341788).||28341788|
|FGFR1 amp||lung cancer||predicted - sensitive||Erdafitinib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Balversa (erdafitinib) inhibited FGFR downstream signaling and proliferation of several lung cancer cell lines with FGFR1 amplification in culture, and inhibited tumor growth in an FGFR1-amplified lung cancer cell line xenograft model (PMID: 28341788).||28341788|