Dasatinib thwarts brain cancer metastasis after bevacizumab use

Combining the antiangiogenic agent bevacizumab (Avastin) with the kinase inhibitor dasatinib (Sprycel) stopped the lethal metastasis of glioblastoma multiforme after initially shrinking the tumors, a mouse study has demonstrated.

Bevacizumab therapy can provide significant but temporary clinical benefit in persons with recurrent glioblastoma, acknowledged Panos Z. Anastasiadis, PhD, chair of the Department of Cancer Biology at Mayo Clinic in Jacksonville, Florida, and colleagues in their report for PLOS One. The drug causes these brain tumors to shrink by depriving them of blood nutrients, but certain proteins help the cancer cells migrate to blood vessels in other parts of the brain in search of more nutrients. This invasion of tumor cells limits the efficacy of surgical and radiological therapies, and patients often deteriorate rapidly once the tumor recurs.

This bevacizumab-induced invasion and aggressiveness is not limited to brain cancer, according to Anastasiadis. “While Avastin offers a clear benefit in some patients, oncologists have noted that when cancers of many types recur after use of Avastin, they become aggressive and invasive,” he explained in a Mayo Clinic statement.

Upon researching the effects of bevacizumab on tumor biology, Anastasiadis and his fellow researchers discovered that as glioblastoma became more aggressive in mice that had been given the drug, the tumor began inducing kinases known as Src. Src in turn activated the proteins that helped the tumor cells move toward a new source of nutrition.

Dasatinib, used in the treatment of chronic myeloid leukemia (CML), inhibits Src kinases. When paired with bevacizumab in the mouse model, dasatinib was able to block subsequent metastasis after bevacizumab shrank the tumors.

The authors contended that these results support the testing of this drug combination in persons with glioblastomas to delay the development of bevacizumab resistance.
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