How Relacorilant Works and Explaining Biomarker-Directed Therapy

Ritu Salani, MD, MBA, of the David Geffen School of Medicine at UCLA, explains to Rachel N. Grisham, MD, of Memorial Sloan Kettering Cancer Center, how she describes the mechanism of relacorilant to patients with platinum-resistant ovarian cancer. Cortisol, the body's stress hormone, signals through the glucocorticoid receptor and makes tumor cells less sensitive to chemotherapy; blocking that receptor restores sensitivity. Relacorilant alone would likely have little activity, but paired with a taxane, the most synergistic class, it makes cancer cells more responsive. She adds that blocking glucocorticoid signaling also appears to boost the immune system by increasing tumor antigen presentation and reducing the immune suppression cancer causes, which may enable future combinations. When counseling patients on biomarker-directed versus biomarker-agnostic therapy, Salani frames it as the biologic rationale: higher expression may improve the odds of response but never guarantees it. She also retests biomarkers at recurrence, since tumors can change and a new positive result can add a treatment option.