Drug Target for Triple-Negative Breast Cancer Found in New Study
Drugs Acting on Newly Identified Protein Are Already in Development
By Jennifer O'Brien | UCSF.edu | October 24, 2016
A team of researchers led by UC San Francisco scientists has identified a new drug target for triple-negative breast cancer, an aggressive disease subtype that has the poorest outcomes and accounts for as many as one in five cases. The findings are particularly noteworthy because drugs that act on the newly discovered target, a protein known as PIM1, are already in clinical trials for leukemia and multiple myeloma.
Triple-negative cancers are so called because they do not express receptors for the hormones estrogen and progesterone, nor for HER2 (human epidermal growth factor 2), and hence patients with these cancers are not candidates for treatment with modern hormonal therapies or the highly effective HER2-targeted drug Herceptin (trastuzumab).
“I’m a breast oncologist, and I’ve seen too many patients die from triple-negative disease,” said senior author Andrei Goga, MD, PhD, professor of cell and tissue biology and of medicine at UCSF, and a member of the Helen Diller Family Comprehensive Cancer Center. “The only treatment we have to offer these patients is chemotherapy, and we desperately need new options.”
The new study, published October 24, 2016 in Nature Medicine, focused on triple-negative breast cancer also characterized by high levels of a cancer-driving protein called MYC (pronounced “mick”). This strategy grew out of previous work in the Goga’s laboratory showing that MYC expression is disproportionately higher in triple-negative tumors than in tumors expressing hormone receptors and/or HER2.
Just as triple-negative cancers present a therapeutic challenge, MYC expression in tumors is also a conundrum. MYC’s role in cancer was discovered more than 30 years ago in the laboratory of UCSF Nobel laureate and Chancellor Emeritus J. Michael Bishop, MD, and it has since been implicated in many aggressive cancers. But, because of its physical characteristics and its fundamental role in normal cellular function, MYC has long been considered an “undruggable” protein.
To get around this problem, the research team employed an approach to undruggable proteins known as “synthetic lethality,” which involves discovering the other proteins upon which these pharmacologically intractable proteins crucially depend to drive cancer growth.