Antitumor Activity of Lenvatinib (E7080): An Angiogenesis Inhibitor That Targets Multiple Receptor Tyrosine Kinases in Preclinical Human Thyroid Cancer Models
Osamu Tohyama,Junji Matsui,Kotaro Kodama,Naoko Hata-Sugi,Takayuki Kimura,Kiyoshi Okamoto,Yukinori Minoshima,Masao Iwata,Yasuhiro Funahashi +8 more
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TLDR
Data demonstrate that lenvatinib provides antitumor activity mainly via angiogenesis inhibition but also inhibits FGFR and RET signaling pathway in preclinical human thyroid cancer models.Abstract:
Inhibition of tumor angiogenesis by blockading the vascular endothelial growth factor (VEGF) signaling pathway is a promising therapeutic strategy for thyroid cancer. Lenvatinib mesilate (lenvatinib) is a potent inhibitor of VEGF receptors (VEGFR1–3) and other prooncogenic and prooncogenic receptor tyrosine kinases, including fibroblast growth factor receptors (FGFR1–4), platelet derived growth factor receptor α (PDGFRα), KIT, and RET. We examined the antitumor activity of lenvatinib against human thyroid cancer xenograft models in nude mice. Orally administered lenvatinib showed significant antitumor activity in 5 differentiated thyroid cancer (DTC), 5 anaplastic thyroid cancer (ATC), and 1 medullary thyroid cancer (MTC) xenograft models. Lenvatinib also showed antiangiogenesis activity against 5 DTC and 5 ATC xenografts, while lenvatinib showed in vitro antiproliferative activity against only 2 of 11 thyroid cancer cell lines: that is, RO82-W-1 and TT cells. Western blot analysis showed that cultured RO82-W-1 cells overexpressed FGFR1 and that lenvatinib inhibited the phosphorylation of FGFR1 and its downstream effector FRS2. Lenvatinib also inhibited the phosphorylation of RET with the activated mutation C634W in TT cells. These data demonstrate that lenvatinib provides antitumor activity mainly via angiogenesis inhibition but also inhibits FGFR and RET signaling pathway in preclinical human thyroid cancer models.read more
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Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial
Masatoshi Kudo,Richard S. Finn,Shukui Qin,Kwang Hyub Han,Kenji Ikeda,Fabio Piscaglia,Ari David Baron,Joong-Won Park,Guohong Han,Jacek Jassem,Jean-Frédéric Blanc,Arndt Vogel,Dmitry Komov,T.R. Jeffry Evans,Carlos Lopez,Corina E. Dutcus,Matthew Guo,Kenichi Saito,Silvija Kraljevic,Toshiyuki Tamai,Min Ren,Ann-Lii Cheng +21 more
TL;DR: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma and the safety and tolerability profiles of lenvatinIB were consistent with those previously observed.
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Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors
TL;DR: The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity and the current landscape of the Shh-SMO-GLI pathway inhibitors including those in preclinical studies and clinical trials is detailed.
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Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer
Vicky Makker,Matthew H. Taylor,Carol Aghajanian,Ana Oaknin,James W. Mier,Allen Lee Cohn,Margarita Romeo,Raquel Bratos,Marcia S. Brose,Christopher DiSimone,Mark Messing,Daniel E. Stepan,Corina E. Dutcus,Jane Wu,Emmett V. Schmidt,Robert Orlowski,Pallavi Sachdev,Robert Shumaker,Antonio Casado Herraez +18 more
TL;DR: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status.
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FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review)
TL;DR: The dual inhibition of FGF and CSF1 or VEGF signaling is expected to enhance the antitumor effects through the targeting of immune evasion and angiogenesis in the tumor microenvironment.
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Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies
Eleonora Molinaro,Cristina Romei,Agnese Biagini,Elena Sabini,Laura Agate,Salvatore Mazzeo,Gabriele Materazzi,Stefano Sellari-Franceschini,Alessandro Ribechini,Liborio Torregrossa,Fulvio Basolo,Paolo Vitti,Rossella Elisei +12 more
TL;DR: The most recent literature regarding conventional, newly available and future therapies for ATC is discussed, and insight into the molecular biology of this disease is provided.
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