Research ArticleCancer

Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy

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Science Translational Medicine  18 Mar 2015:
Vol. 7, Issue 279, pp. 279ra40
DOI: 10.1126/scitranslmed.aaa4642

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A more refined antitumor strategy

The BCL-2 family is a group of related proteins that regulate apoptosis in a variety of ways. The success of anticancer treatments often hinges on the ability to induce cancer cell death by apoptosis. As a result, there has been a great deal of interest in developing drugs that can inhibit the antiapoptotic members of the BCL-2 pathway. Unfortunately, some of these drugs are also associated with dose-limiting hematologic toxicities, such as neutropenia. Now, Leverson et al. have used a toolkit of BCL-2 family inhibitors with different specificities to show that specifically inhibiting BCL-XL (one member of this protein family) is effective for killing tumors, but without the common side effects seen with less selective drugs.