Target found for triple negative breast cancer

College of Natural Resources researchers have found a long-elusive Achilles’ heel within “triple-negative” breast tumors, a common type of breast cancer that is difficult to treat. Such cancers account for about one in five instances of the disease, and they are deadlier than other forms of breast cancer, in part because no drugs have been developed to specifically target their tumors.

“We were looking for targets that drive cancer metabolism in triple-negative breast cancer, and we found one that was very specific to this type of cancer,” said Daniel K. Nomura, an associate professor of nutritional sciences and toxicology (NST) and of chemistry. Nomura was the senior author for the study, which was published in Cell Chemical Biology last spring.

Tumor cells develop an abnormal metabolism, which they rely on to get the energy boost they need to fuel their rapid growth. In its study, Nomura’s research team used an innovative approach to search for active enzymes that triple-negative breast cancers use differently for metabolism than other cells and even other tumors.

The team discovered that triple-negative breast cancer cells rely on vigorous activity by an enzyme called glutathione-S-transferase Pi1. The scientists then used a drug-like molecule named LAS17 to successfully target this vulnerability, killing cancer cells in the lab and shrinking tumors in mice.

The team intends to continue studying LAS17, Nomura said, the next step being to study tumor tissue resected from human triple-negative breast cancers and transplanted directly into mice.

The study’s authors also included NST’s Sharon Louie, Elizabeth Grossman, Lucky Ding, Tucker Huffman, and David Miyamoto; Roman Camarda and Andrei Goga of UC San Francisco; and Eranthie Weerapana and Lisa Crawford of Boston College.