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Hereditary Papillary Renal Cell Cancer
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
For advanced or disseminated RCC, radical nephrectomy (removal of an entire affected kidney) may be necessary. Locoregional therapy (e.g., antivascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitors [TKI] sunitinib, pazopanib, and foretinib, and mammalian target of rapamycin [mTOR] inhibitor temsirolimus) may help reduce tumor size and palliate symptoms, while systemic therapy shows only limited efficacy [16]. Kidney transplantation may be considered for patients with severe kidney dysfunction. Currently, the 5-year living donor graft survival rate stands at nearly 90%.
Investigational MET inhibitors to treat Renal cell carcinoma
Published in Expert Opinion on Investigational Drugs, 2019
Lakshminarayanan Nandagopal, Guru P. Sonpavde, Neeraj Agarwal
Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL and TIE-2 receptors [57]. Its ability for concurrent MET inhibition can overcome resistance to anti-VEGF therapy and has demonstrated superior efficacy in inhibiting angiogenesis compared to restricted VEGF blockade in preclinical models [58]. In a phase 1 study in 40 patients with advanced solid tumors, 2/4 patients with pRCC had partial response (PR) with prolonged duration of response – 48 and 12 months, respectively [59]. It had acceptable tolerability with notable side effects being AST elevation and hypertension. The final recommended dose was 240 mg given on the first 5 days of a 14-day cycle. Another phase 1 study determined 80 mg daily given continuously as an alternative dosing regimen [60].
MET inhibitors in cancer: pitfalls and challenges
Published in Expert Opinion on Investigational Drugs, 2020
Helena Oliveres, Estela Pineda, Joan Maurel
Foretinib is an orally available small-molecule inhibitor. It targets receptor tyrosine kinases: MET, RON, ERK, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AKT, FMS-like tyrosine kinase 3 (FLT3), angiopoietin receptor (TIE-2) and RET kinases. A first-in-human study in 40 metastatic or unresectable solid tumors showed hypertension, fatigue, diarrhea, vomiting, proteinuria, and hematuria as side-effects. The recommended dose of foretinib was 240 mg, given on the first 5 days of a 14-day cycle [43]. Three patients obtained partial response (8%).
Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors
Published in Expert Review of Anticancer Therapy, 2018
Assunta Sgambato, Francesca Casaluce, Paolo Maione, Cesare Gridelli
Recently, another potent inhibitor against ROS1 who overcomes resistance mutations including G2032R was identified in foretinib, which is an oral multi-kinase inhibitor targeting MET, VEGFR-2, RON, KIT, and AXL kinases. From preclinical data, foretinib confirmed as inhibitor of wild type and all mutated crizotinib-resistance ROS1 fusions [59]. Although the difficult comparator between the plasma concentrations and expected efficacy in humans, foretinib seems to be less potent and effective than cabozatinib and the clinical development was stopped.