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A Deeper Look

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A new study published in Cancer Cell by researchers at the Broad Institute and the Dana-Farber Cancer Institute focuses on the cancer gene MCL1, according to a Broad press release. MCL1 inhibits apoptosis, and it is one of the most commonly mutated genes in several different kinds of cancer. The study highlights several compounds that repress MCL1. In addition, the Broad says, the study reports a companion gene, BCL-xL, that can help predict whether a specific tumor is dependent on MCL1 for its survival. "It was not immediately obvious that MCL1 was such an attractive therapeutic target in cancer," says the Broad's Todd Golub. "But once it became clear that MCL1 was something that we wanted to turn off in tumor cells, we faced two additional problems: we didn't know which tumors depend on it for survival and there wasn't an obvious path to drug discovery. This paper addresses those two challenges."

The researchers started by suppressing MCL1 in several cancer cell lines to determine which ones were dependent on the gene. They then looked for a marker that could predict which cell lines were dependent, and found that BCL-xL was the clearest indicator, the Broad says. The team also tested about 3,000 compounds to search for ones that turned off MLC1 in cancer cells, and found some that could serve as a starting point towards developing a drug specifically to target MCL1.

The Scan

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