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Reprogramming Cancer

Glioblastomas are the most common brain tumors. They are also the most lethal, in part because of a small population of stem cells that live inside each tumor. Although the stem cells comprise only a small portion of the tumor—just a few percent—they are not trivial. They cause aggressive tumor growth as well as resistance to radiation and chemotherapy. Recent findings by HHMI scientists point to a way to disarm these cells by focusing on what makes them so different from the rest of the tumor.

Early Career Scientists Bradley Bernstein, at Massachusetts General Hospital, and Aviv Regev, at Massachusetts Institute of Technology, collaborated to examine the circuits that regulate genes in both stem cells and non-stem cells from glioblastoma tumors. The researchers found four transcription factors—proteins that turn genes on and off—that were present only in the stem cells. When they expressed a cocktail of four transcription factors in the non-stem cells from the glioblastomas, those cells turned into stem cells. The experiments, published April 24, 2014, in Cell, show that transcription factors can override a glioblastoma cell’s programming and drive it into a more aggressive state.

Bernstein and Regev hope to use this information to target these aggressive stem cells with small molecule inhibitors.