Fruquintinib (HMPL-013) strongly inhibits VEGFR1
, 2 and 3.
Aflibercept (VEGF-Trap) is an engineered soluble receptor made from the extracellular domains of VEGFR1
and VEGFR2 and binds to all isoforms of VEGF and to placental growth factor.
Two related receptors facilitate VEGF signalling: VEGFR1
(Flt-1) which is thought to act as a decoy receptor and VEGFR2 (KDR) which mediates the pro-angiogenic signal.
For example, Sirna is investigating the regulation of angiogenesis in AMD by targeting multiple VEGF receptors -- VEGFR1
and VEGFR2 -- using a single siRNA molecule.
To identify potential subgroups of rectal cancer patients who might benefit from cetuximab-based neoadjuvant radiochemotherapy, we assessed gene expression of factors involved in tumor growth (EGFR), angiogenesis (VEGF, VEGFR1
, VEGFR2d), DNA repair (ERCC1) and drug metabolism (TS), as well as KRAS gene mutation status.
58) In addition to KIT and PDGFR, it targets VEGFR1
and VEGFR2, FLT3, and RET.
also is implicated in the development and progression
Furthermore, TAMs express VEGFR1
(flt1)  and respond to its activation by migrating and modulating their biological activity in response to VEGFR1
ligands  such as VEGF produced by tumour cells.
These data provide the foundation for developing a new diagnostic test for improving a) chemotherapy response for bladder cancer patients; and b) defining new gene combinations that may help predict clinical benefit from chemotherapy of colorectal cancer, specifically the association between KRAS status, gene expression levels of VEGFR-2, ERCC1 and EGFR with clinical outcome to chemotherapy combination 5-FU, oxaliplatin and bevacizumab (FOLFOX/BV) therapy in patients with metastatic colorectal cancer; and c) showing that VEGF and VEGFR1
gene expression levels may predict tumor recurrence risk in colon cancer patients and help identify patients likely to benefit from adjuvant chemotherapy.
Fruquintinib is designed as a highly selective and potent oral inhibitor of vascular endothelial growth factor ("VEGF") receptors ("VEGFR"), namely VEGFR1
, VEGFR2, and VEGFR3.