Psychosocial Stress, Glucocorticoid Signaling, and Prostate Cancer Health Disparities in African American Men

Recent advances in our understanding of racial disparities in prostate cancer (PCa) incidence and mortality that disproportionately affect African American (AA) men have provided important insights into the psychosocial, socioeconomic, environmental, and molecular contributors. There is, however, li...

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Bibliographic Details
Published inCancer health disparities Vol. 4
Main Authors Woods-Burnham, Leanne, Stiel, Laura, Martinez, Shannalee R, Sanchez-Hernandez, Evelyn S, Ruckle, Herbert C, Almaguel, Frankis G, Stern, Mariana C, Roberts, Lisa R, Williams, David R, Montgomery, Susanne, Casiano, Carlos A
Format Journal Article
LanguageEnglish
Published United States 2020
Subjects
African ancestry
glucocorticoid receptor
prostate cancer
health disparities
psychosocial stress
clinical trials
glucocorticoid signaling
African American
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Summary:Recent advances in our understanding of racial disparities in prostate cancer (PCa) incidence and mortality that disproportionately affect African American (AA) men have provided important insights into the psychosocial, socioeconomic, environmental, and molecular contributors. There is, however, limited mechanistic knowledge of how the interplay between these determinants influences prostate tumor aggressiveness in AA men and other men of African ancestry. Growing evidence indicates that chronic psychosocial stress in AA populations leads to sustained glucocorticoid signaling through the glucocorticoid receptor (GR), with negative physiological and pathological consequences. Compelling evidence indicates that treatment of castration-resistant prostate cancer (CRPC) with anti-androgen therapy activates GR signaling. This enhanced GR signaling bypasses androgen receptor (AR) signaling and transcriptionally activates both AR-target genes and GR-target genes, resulting in increased prostate tumor resistance to anti-androgen therapy, chemotherapy, and radiotherapy. Given its enhanced signaling in AA men, GR-together with specific genetic drivers-may promote CRPC progression and exacerbate tumor aggressiveness in this population, potentially contributing to PCa mortality disparities. Ongoing and future CRPC clinical trials that combine standard of care therapies with GR modulators should assess racial differences in therapy response and clinical outcomes in order to improve PCa health disparities that continue to exist for AA men.
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Authors’ contributions
L.W.B., L.S., S.M., and C.A.C. contributed to the conceptual design of the original research topic. L.W.B. wrote the initial version of the manuscript and prepared Fig. 1. S.R.M. wrote the sections on GR biology. H.R.C. contributed to the section on prostate cancer treatment options. F.G.A. wrote the section on PSMA theranostics. E.S.S.H. prepared Figs. 2, 3, and 4, and cross-checked for accuracy the literature citations throughout the manuscript. M.C.S., L.R.R., and D.R.W. provided unique perspectives that guided the writing of sections related to socioeconomic and psychosocial aspects of PCa. L.W.B., L.S., and C.A.C. edited the various drafts of the manuscript. All authors reviewed and approved the manuscript prior to submission.
Current Address: City of Hope Comprehensive Cancer Center, Department of Population Sciences, Division of Health Equities, 1500 East Duarte Rd, Duarte CA 91010
ISSN:2573-9530