Rogaratinib: A potent and selective pan‐FGFR inhibitor with broad antitumor activity in FGFR‐overexpressing preclinical cancer models

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<jats:p>Aberrant activation in fibroblast growth factor signaling has been implicated in the development of various cancers, including squamous cell lung cancer, squamous cell head and neck carcinoma, colorectal and bladder cancer. Thus, fibroblast growth factor receptors (FGFRs) present promising targets for novel cancer therapeutics. Here, we evaluated the activity of a novel pan‐FGFR inhibitor, rogaratinib, in biochemical, cellular and <jats:italic>in vivo</jats:italic> efficacy studies in a variety of preclinical cancer models. <jats:italic>In vitro</jats:italic> kinase activity assays demonstrate that rogaratinib potently and selectively inhibits the activity of FGFRs 1, 2, 3 and 4. In line with this, rogaratinib reduced proliferation in FGFR‐addicted cancer cell lines of various cancer types including lung, breast, colon and bladder cancer. FGFR and ERK phosphorylation interruption by rogaratinib treatment in several <jats:italic>FGFR</jats:italic>‐amplified cell lines suggests that the anti‐proliferative effects are mediated by FGFR/ERK pathway inhibition. Furthermore, rogaratinib exhibited strong <jats:italic>in vivo</jats:italic> efficacy in several cell line‐ and patient‐derived xenograft models characterized by <jats:italic>FGFR</jats:italic> overexpression. The observed efficacy of rogaratinib strongly correlated with <jats:italic>FGFR</jats:italic> mRNA expression levels. These promising results warrant further development of rogaratinib and clinical trials are currently ongoing (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://clinicaltrials.gov">ClinicalTrials.gov</jats:ext-link> Identifiers: NCT01976741, NCT03410693, NCT03473756).</jats:p>

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