Exelixis, Inc. (NASDAQ:EXEL) today announced the company's lead compound, cabozantinib, is highlighted in a new peer-reviewed publication demonstrating that simultaneous inhibition of MET and VEGF signaling reduces tumor invasiveness and metastasis in preclinical models of pancreatic cancer. The research, led by Dr. Donald M. McDonald at the University of California, San Francisco (UCSF), showed that selective inhibition of VEGF signaling with a neutralizing antibody against VEGF or with a small molecule kinase inhibitor resulted in more invasive and metastatic tumors than from placebo-treated mice. Importantly, this effect was accompanied by increased expression of MET. The researchers went on to show that treatment with cabozantinib (which targets both MET and VEGF signaling), or with a combination of selective inhibitors targeting both pathways, reduced these malignant processes. The researchers also reported that cabozantinib prolonged survival compared with all other treatment combinations examined.
The preclinical data will be published in the March 1, 2012 issue of Cancer Discovery and are also discussed in a press release issued by the American Association for Cancer Research, the journal's publisher. Starting today, the article will be available at http://cancerdiscovery.aacrjournals.org. Researchers at Exelixis collaborated on the studies with UCSF.
"These data provide important insights into the potential clinical benefits of simultaneously inhibiting the MET and VEGF signaling pathways with cabozantinib, and add to the scientific rationale for our ongoing clinical investigation of the compound," said Michael M. Morrissey, Ph.D., president and chief executive officer at Exelixis. "To date, cabozantinib has shown activity in 12 of 13 tumor types studied, including particularly encouraging interim results in castration-resistant prostate, medullary thyroid, renal, liver, ovarian, non-small cell lung, and breast cancers, as well as melanoma. These results suggest that, in many types of tumors, cabozantinib may have a potentially differentiated activity profile as compared to compounds that inhibit only VEGF or MET."
In the research described in Cancer Discovery, tumor-bearing mice were treated with an anti-VEGF antibody or with sunitinib, which inhibits multiple tyrosine kinases including VEGF receptors. These treatments were tested alone or in combination with an inhibitor of MET. Separate groups of animals were treated with cabozantinib. Key findings include: