Studies Uncover Surprising Roles for Glucocorticoids in Cancer
Desai Sethi Urology Institute Scientific Director Nima Sharifi, M.D., authored papers in Nature and the New England Journal of Medicine that look at the role of glucocorticoids in glioblastoma and breast cancer. This research reflects the Sharifi Lab’s extensive work in metabolism and cancer progression.
Two recent papers published in high-impact journals Nature and the New England Journal of Medicine have two things in common.
Nima Sharifi, M.D., scientific director and professor of urology at Desai Sethi Urology Institute (DSUI) and a member of Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, is an author on both. And while the topics are on completely different cancer types, they tie into an extensive body of research at the Sharifi Lab on steroid hormone metabolism and its impact on disease and physiology.
“Our group has a track record of work on steroids and the chemistry of steroids, and we have collaborations with researchers around the world to study metabolism’s impact on individual cancers, including prostate, breast and brain,” Dr. Sharifi said.
Glucocorticoid Focus
There are distinct categories of steroid hormones, including androgens, which we usually associate with prostate cancer, and estrogens in breast cancer.
“It turns out, another steroid hormone is linked to cancer. Glucocorticoids stimulate the glucocorticoid receptor, a transcription factor with complex interactions with other steroid receptors relevant to cancer, including androgen receptor and estrogen receptor alpha,” Dr. Sharifi said.
These papers point to surprising ways in which glucocorticoids may impact cancer treatment and outcomes.
Fasting, Glucocorticoids and Breast Cancer
Dr. Sharifi, author of an article on clinical implications of basic research in the New England Journal of Medicine, offered a perspective on a previously published study suggesting that fasting can increase glucocorticoids, potentially accentuating the effect of anti-estrogen therapy on breast cancer. It’s possible, then, women with estrogen receptor-positive breast cancer who are on endocrine therapy may benefit from fasting. The previous study’s authors looked at mouse and human studies with weekly cycles of fasting for 48 hours.
“The idea that cancer-associated outcomes can be regulated, at least in part, by fasting and the timing of eating is powerful because it adds a layer of control for patients,” Dr. Sharifi said.
This supports the need for more research.
“We need to understand the specific physiological mechanisms of fasting interventions that are relevant to the biologic characteristics of a tumor in order to design a framework for testing behavioral interventions as adjuvants or alternatives to pharmacologic interventions,” Dr. Sharifi said.
Androgens, Glucocorticoids and Glioblastoma in Men
Testosterone may play a key role in suppressing brain tumor growth in men, and supplemental testosterone might help to improve these patients’ survival, according to a paper authored by Dr. Sharifi and Yoon-Mi Chung, M.S., director of mass spectrometry in the Sharifi Lab, and led by brain tumor researchers at Cleveland Clinic. DSUI’s contribution was to identify the hormonal discordance in brain cancer in men and generate the needed data, using mass spectrometry.
The study found that a loss of androgen hormones, such as testosterone, drove glioblastoma tumor growth by inducing local inflammation and triggering the production of stress hormones, including glucocorticoids.
The surprising discovery helps to understand how sex differences occur and how indirect effects of sex steroids contribute to brain tumor outcomes.
“We found that it isn’t just about androgens, but when you modify androgens you actually regulate glucocorticoids, which also is important for driving outcome differences in brain cancer,” Dr. Sharifi said.
Anthony Letai, M.D., Ph.D., director of the National Institutes of Health’s National Cancer Institute, called the outcome a welcome surprise, which “may potentially offer a lead for new treatments for a kind of cancer that is deadlier in men.”
“These studies help to pave the way for more studies that look at the roles of glucocorticoids and other steroid hormones on these and other cancers, as sex differences in cancer have long been recognized in bladder, colorectal system, lung, skin and brain cancers,” Dr. Sharifi said.
More from the Miller School of Medicine
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Desai Sethi Urology Institute’s Dr. Nima Sharifi and Dr. Zhipeng Wang were named recipients of Prostate Cancer Foundation grants.
Speakers shared research looking at how human metabolism impacts disease at the third annual Miami Symposium on Human Metabolism.
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Tags: brain cancer, breast cancer, cancer research, clinical trials, Desai Sethi Urology Institute, Division of Endocrinology Diabetes and Metabolism, Dr. Nima Sharifi, Hormone and Metabolic Research, prostate cancer, Sylvester Comprehensive Cancer Center, testosterone therapy