Retinoids for the Treatment of Glioblastoma

Abstract

Glioblastoma is the most common malignant brain tumor in adults and it is the most lethal among all cancers. A number of recent studies have suggested that retinoids (vitamin A and its derivatives) are of special interest in the treatment of glioblastoma, owing to their anti-proliferative and cancer-preventative properties. Retinoids are signaling molecules that play important roles in cell growth, differentiation, and death. Retinoids act through two types of receptors – retinoic acid receptors and retinoid X receptors – which themselves act as ligand-dependent transcription factors. Extensive research efforts have been dedicated to elucidating the molecular and cellular networks that are induced by retinoids, and this has recently yielded novel insights into how retinoids can both prevent and combat this brain tumor. Retinoids achieve these objectives by inducing differentiation and/or growth arrest. Although much important data have been obtained, the exact signaling pathways required for retinoids to exert their biological effects remain elusive. In this article, we outline the role and function of retinoid receptors, followed by a discussion of how major signaling pathways are affected in different tumor types after treatment with retinoids. This also focuses on anti-tumor activity of retinoids, their roles in combination chemotherapy, and clinical trials of retinoids in glioblastoma. Studies summarized in this article clearly indicate that retinoids represent a potentially powerful therapeutic choice in the treatment of glioblastoma.