New study may pave the way for targeted cancer treatments

Imagine a drug that halts cancer without side effects or risks. That future may be a bit nearer thanks to recent research led by Raj Kumar, Ph.D., chair of the Department of Pharmaceutical and Biomedical Sciences at Touro College of Pharmacy.

The study is published in the journal Nature Communications.

His lab has been studying steroid hormone receptors (SHRs), one of the most targeted proteins for cancer treatments. Steroid hormones, such as estrogen and testosterone, are targeted because cancer cells have higher-than-normal levels of SHRs, which can fuel breast, prostate, and ovarian cancer. But because these anti-hormone drugs also bind to SHRs in other cells in the body (such as in the uterus and bones), they often cause side effects and risks.

“You’re trying to cure breast cancer, but you’re increasing the effect of estrogen in uterine tissue, which can lead to uterine cancer,” says Kumar.

“The ‘Holy Grail’ of SHR-based therapies for the treatment of endocrine cancers is to restrict SHR actions to specific organ and gene targets,” he says. To do that, we need a better understanding of the structure of SHRs and how they interact with other proteins.

Kumar’s research provides the first detailed look at this steroid hormone receptor complex.

“When we know the whole SHR structure, and how associated proteins form the complex, then we can design a drug that can be specifically targeted to certain tissues,” says Kumar. Differences in the steroid hormone receptor complex are why hormones—and potential medications—act differently in different types of cells and tissues.

A limited understanding of these structures has hampered efforts to develop more effective target-specific drugs with minimal or no side effects. Kumar’s team has teased out differences in these structures using novel proteomics technology.

“To our knowledge, this is the first time we are showing this level of detail in the structure of a steroid hormone receptor coactivator complex,” says Kumar.

“This research will dramatically improve our ability to predictably disrupt steroid hormone receptor signaling and is likely to produce more effective drugs for the treatment of endocrine cancers with minimal or no undesired serious side effects,” he adds.

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