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Pointing toward new brain tumor strategy

Medicine@Yale, 2017 - Apr May


An existing, FDA-approved ovarian cancer drug may also treat brain cancers and leukemias that have mutations in the genes IDH1 and IDH2.

In a new study, led by Ranjit S. Bindra, M.D., Ph.D., assistant professor of therapeutic radiology and of pathology, and Peter M. Glazer, M.D., Ph.D., chair and Robert E. Hunter Professor of Therapeutic Radiology and professor of genetics, the researchers wanted to know why IDH mutations make tumors more susceptible to radiation therapy and chemotherapy.

In the process of studying isolated cancer cells with the mutations, the team discovered that the cells are also sensitive to a class of drugs called PARP inhibitors.

Treating the cells with olaparib, a PARP inhibitor that was approved for use in hereditary ovarian cancer in 2016, killed 50 times more tumor cells than usual. And the drug slowed the growth of tumors on mice by eightfold, the researchers reported Feb. 1 in Science Translational Medicine.

The finding suggests that PARP inhibitors such as olaparib may be effective in treating a range of tumor types with IDH mutations and that blocking mutant versions of IDH—a current approach which would not be compatible with olaparib—may not be the ideal treatment strategy.