Marine-derived steroids for cancer: search for potential selective glucocorticoid receptor agonists modulators (SEGRAM)

Steroids, particularly glucocorticoids, are essential components of cancer treatment for both hematological malignancies and solid tumors. The adverse effects of standard steroid-based drugs have forced drug discovery research to develop chemotherapeutics with a more selective mechanism of action and an improved therapeutic index. Steroids of natural origin and their analogs are a significant source of novel molecules with a wide spectrum of biological activities. In this review, we aimed to analyze marine-derived steroids and their anti-cancer activity. Moreover, we specifically discussed molecules with not only anti-cancer but also anti-inflammatory activities that could potentially mimic the effects of glucocorticoids. We hypothesized that several of the reviewed compounds could exhibit affinity to the glucocorticoid receptor, and possess the properties of selective glucocorticoid receptor agonists/modulators with increased therapeutic activity and decreased side effects. The review is based on the literature available in the PubMed, Cochrane, and ClinicalTrials.gov databases and covers the period from 1986 to 2025. The keywords used were “steroids”, “cancer”, and “marine-derived steroids”. The second iteration of the literature search included the keywords “selective glucocorticoid receptor agonists”, “marine-derived”, and “cancer”. In silico calculations of several marine-derived compounds were performed to support the hypothesis based on the literature data.