Dual VEGF and c-MET Inhibition Synergistically Reduces Tumor Invasion and Metastasis

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(ChemotherapyAdvisor) – Simultaneous inhibition of c-Met and VEGF signaling slowed tumor growth and reduced invasion and metastasis in a pancreatic neuroendocrine mouse model, results of a study published online in Cancer Discovery February 24 have found.

In this study, the investigators “asked whether selective VEGF inhibition is sufficient to increase invasion and metastasis and whether selective c-Met inhibition is sufficient to block this effect.” They tested two inhibitors of VEGF — crizotinib, PF-04217903, and cabozantinib (XL184). Cabozantinib simultaneously inhibits both c-MET and VEGF.

They found that concurrent inhibition of c-Met by PF-04217903 or crizotinib reduced invasion and metastasis. A similar benefit was found in orthotopic Panc-1 pancreatic carcinomas treated with sunitinib plus PF-04217903 and in RIP-Tag2 tumors treated with cabozantinib.

The two-target approach may have broad application for treating a wide variety of cancers. While clinical trials are underway to gauge effectiveness of the approach in humans with prostate cancer, breast cancer, and other tumor types, this is the first study to demonstrate how the drug combination works in the laboratory.


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