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Sandy Srinivas, MD


Can the Corticosteroid Betamethasone Improve Outcomes With Radiation Therapy for Prostate Cancer?

By: Julia Fiederlein
Posted: Friday, September 9, 2022

The expression of the RelB/B-cell linker protein (BLNK) axis may identify patients with prostate cancer who may potentially respond to treatment with redox-active agents during radiation therapy, according to Luksana Chaiswing, PhD, of the University of Kentucky, Lexington, and colleagues. The results of this analysis, which were published in the International Journal of Molecular Sciences, couple the novel concept of redox therapy with the glucocorticoid betamethasone to precision medicine.

“The outcome of this project could lead to a new anticancer regimen that improves the efficacy of radiation therapy by sensitizing tumor tissue to radiation while simultaneously protecting normal tissue from radiation-induced side effects,” commented Dr. Chaiswing in an institutional press release. “[This] could lead to improved quality of life for cancer survivors.”

The investigators defined criteria for compound selection: protection of noncancer cells against radiation therapy–induced cytotoxicity; death of prostate cancer cells; and an increased level of hydrogen peroxide in both prostate cancer and noncancer cells. Betamethasone was found to significantly increase the levels of reactive oxygen species. In normal cells, betamethasone seemed to induce protein expression of RelB and RelB target genes, including manganese superoxide dismutase; however, it appeared to suppress protein expression of RelB and manganese superoxide dismutase in androgen-responsive and androgen-independent prostate cancer cells.

RNA-sequencing analysis identified BLNK as a novel RelB complementary partner that is differentially regulated by betamethasone in noncancer and prostate cancer cells. According to the investigators, RelB and BLNK are upregulated and correlate with the aggressiveness of prostate cancer in human samples. Manganese superoxide dismutase protein expression was found to be activated via the translocation of the RelB/BLNK axis to the nuclear compartment. Betamethasone seemed to promote the RelB/BLNK axis in noncancer cells and to suppress it in prostate cancer cells. Targeted disruptions of RelB/BLNK expression appeared to mitigate the radioprotective and radiosensitizing effects of betamethasone on noncancer and prostate cancer cells, respectively.

Disclosure: The study authors reported no conflicts of interest.

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