Researchers Win $1.4 Million Grant to Develop New Ways to Block Breast Cancer

By Eric Sauter

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have received a $1.4 million grant from the Department of Defense to develop a series of drug candidates that act against molecules closely linked with the growth of cancer cells.

Donald G. Phinney, a TSRI professor and acting chairman of the Department of Molecular Therapeutics, is the principal investigator of the new three-year grant.

“The focus of our research will be on breast cancer,” Phinney said. “We’re targeting a specific microRNA—microRNAs don’t produce proteins but can still regulate gene expression—because of its pivotal role in breast cancer. By blocking it, we think we can stop or, at the very least, impede tumor growth, with less toxicity than is often associated with chemotherapy.”

Recent research has shown that virtually all cancer cells experience what is known as “hypoxic stress”—periods of low oxygen. But cancer cells can adapt by slowing their growth rate and metabolism, which increases the cells’ ability to survive. Adaptation to hypoxia is now seen as critical to tumor growth, metastasis and development of drug resistance.

The microRNA that is the focus of the new study is induced by low oxygen and plays a vital role in breast cancer cells’ adaptation to that stressful environment.

“Some preliminary studies have shown that inhibition of this microRNA increases the sensitivity of these incipient cancer cells to hypoxia-induced death and makes drug-resistant cancer cells more vulnerable to chemotherapy with low toxicity,” Phinney said. “Moreover, drugs that target microRNAs provide more durable and potent effects precisely because they attack entire pathways disrupted by cancer, as opposed to drugs that target a single protein, which are susceptible to drug resistance.”

The approach taken in the new study is broad enough to identify and target a number of different microRNAs implicated in breast and other cancers. This work is being done in collaboration with TSRI Professor Matthew Disney, who has pioneered the development of RNA-targeting drug therapies. 

The number of the new grant is W81XWH-16-1-0029.

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