<p>Fruquintinib: a novel antivascular endothelial growth factor receptor tyrosine kinase inhibitor for the treatment of metastatic colorectal cancer</p>

Abstract

Angiogenesis plays a critical role in the neoplastic growth, progression, and metastasis of colorectal cancer (CRC) in a process regulated by vascular endothelial growth factor (VEGF) family members and their receptors (VEGFR). Several small-molecule anti-VEGFR tyrosine kinase inhibitors (TKIs), such as regorafenib, famitinib, axitinib and apatinib, have been shown to be effective in treating metastatic colorectal cancer (mCRC). Fruquintinib (ELUNATE ® ) is a novel oral anti-VEGFR TKI, originated and developed by Hutchison MediPharma. Fruquintinib is a potent and highly selective small-molecule inhibitor of VEGFR-1, -2 and -3. In the Phase 3 FRESCO trial, fruquintinib improved both overall survival (OS) and progression-free survival (PFS) in patients with mCRC, compared with placebo. Fruquintinib also showed an acceptable safety and tolerability profile. Based on the data from this trial, fruquintinib was approved by the China Food and Drug Administration (CFDA) in 2018, for the treatment of patients with mCRC who had undergone at least two prior standard anticancer therapies. The existing clinical trials and future prospects of fruquintinib in mCRC will be discussed in this article. In addition, to better understand the role of fruquintinib in this setting, recent advances in other anti-VEGFR TKIs for mCRC treatment are also reviewed herein.

Synthesis of novel bis‐ and poly(benzimidazoles) as well as bis‐ and poly(benzothiazoles) as anticancer agents

“…To investigate the binding modes of the most active compounds 18a , 20a , 20b , 22a , 22b and 24 with the active sites of vascular endothelial growth factor receptor‐2 (VEGFR‐2), molecular docking was performed by Molecular Operating Environment software (MOE 2014.0901) . As per literature, inhibition of the signaling pathway of VEGFR‐2 can be considered as a promising strategy to fight cancer disease . The crystal structure of VEGFR‐2 protein was obtained from the Protein Data Bank (PDB ID: 2XIR).…”

Molecular-targeted therapy toward precision medicine for gastrointestinal caner: Current progress and challenges

“…Axitinib, a first-generation anti-VEGFR TKI with high potency against VEGFRs, platelet-derived growth factor receptor (PDGFR) and c-KIT, has been approved by the FDA for the treatment of renal cell carcinoma[ 40 ]. In phase II trials, the median PFS was significantly increased in the axitinib group compared to the placebo group (4.9 mo vs 3.1 mo; P = 0.0116) for patients with first-line mCRC, suggesting that axitinib is a promising candidate for the maintenance treatment of mCRC[ 41 ]. Fruquintinib, a novel oral TKI of VEGFR-1, -2 and -3, afforded significantly superior median OS (HR: 0.65, P < 0.001) and median PFS (HR: 0.26, P < 0.001) compared to placebo in patients with chemo-refractory mCRC, and it demonstrated the benefit of VEGFR inhibition in the latter lines of mCRC treatment[ 42 ].…”

Tyrosine Kinase Receptors in Oncology

“…The results of a phase III with rivoceranib failed to show benefit in OS but the result of secondary endpoints as PFS were positive, and the drug is under FDA evaluation for approval [ 278 ]. In a similar way, fruquintinib is approved in China for the treatment of advanced colorectal cancer and anlotinib for the treatment of non-squamous cell lung cancer [ 279 , 280 ].…”