Adelaiye-Ogala Awarded NCI Grant to Study Prostate Cancer

By Dirk Hoffman

The National Institutes of Health R01 grant is titled “Posttranslational Modifications of Glucocorticoid Receptor Associated With Drug-Resistance in Prostate Cancer.”

Most prostate cancer deaths occur in men with advanced prostate cancer that has become resistant to current treatments, including androgen receptor (AR)-targeted therapies, according to Adelaiye-Ogala, who works in the Division of Hematology/Oncology.

“The glucocorticoid receptor (GR) has emerged as a focus for developing inhibitors/modulators that block its activity by competitively binding to its hormone-binding site,” she says. “However, GR can also be activated through mechanisms independent of this site.”

Adelaiye-Ogala says her study aims to understand these alternative activation pathways, specifically focusing on how posttranslational modifications activate GR as an oncogene in advanced prostate cancer.

“Our objectives are to understand the specific traits and how a modified glucocorticoid receptor behaves at the molecular level in aggressive prostate cancer and to use this knowledge to identify effective treatment approaches,” she says.

Activating the compensatory signaling pathway for survival is common in cancers, especially prostate cancer, and GR activity as a compensatory nuclear hormone receptor for survival has been observed in advanced prostate cancers, says Adelaiye-Ogala, who is also a clinical assistant professor of urology.

A phase 1 clinical study has shown that combining GR modulators (relacorilant) with standard of care (enzalutamide) delayed resistance to enzalutamide. However, not all patients’ tumors respond, she adds.

“Our research will help create precise and effective treatments for this subpopulation of patients that are safe and improve outcomes for men with high-risk, advanced prostate cancer.”

Adelaiye-Ogala is principal investigator on the grant, but has multiple collaborators within and outside of the University at Buffalo.

Co-investigators from UB are:

• Roberto Pili, MD, professor of medicine and chief of the Division of Hematology/Oncology at the Jacobs School of Medicine and Biomedical Sciences
  
• Jeffery Miecznikowski, PhD, professor of biostatistics in UB’s School of Public Health and Health Professions
  

Co-investigators/collaborators from outside of UB are:

• Suzanne D. Conzen, MD, professor of internal medicine and chief of the Division of Hematology and Oncology at UT Southwestern Medical Center, Dallas, Texas
  
• David J. VanderWeele, MD, PhD, associate professor in medicine-hematology/oncology at  Northwestern University Feinberg School of Medicine, Chicago, Illinois 
  
• Russell Zelig Szmulewitz, MD, associate professor of medicine, director of the genitourinary oncology program and associate director for clinical investigation at the comprehensive cancer center at the University of Chicago, Chicago, Illinois
  

“Together, we plan to achieve the overarching goal of this study, which is to develop precise and effective treatments that are safe and improve outcomes for men with high-risk and lethal prostate cancers,” Adelaiye-Ogala says.