2 - A carrot a day keeps recurrence away! The use of vitamin A and its metabolic products in the circumvention of cisplatin resistance via Aldehyde Dehydrogenase 1 (ALDH1)

Abstract

Despite advances in personalised medicine, cisplatin remains the mainstay in NSCLC management, however the develop-ment of pan-resistance to platinum agents has become a major clinical challenge. Novel drug design, preclinical and clinical trials working toward the approval of new drugs is a lengthy and costly process and in the interim research has turned its focus to overcoming resistance and repurposing drugs. Cancer stem cells (CSCs) have been hypothesised to be the initiating cells of resistance and recurrence. ALDH1-positive cells have been identified as a CSC subpopulation within cisplatin resistant (CisR) NSCLC sublines. ALDH1 converts retinal to retinoic acid during the metabolism of retinol (vitamin A), retinoic acid induces cell differentiation. All-trans retinoic acid (ATRA) is a well-established chemotherapeutic agent in the treatment of acute promyelocytic leukaemia; it induces the terminal differentiation of immature cells. We hypothesise that retinol and ATRA will deplete the ALDH1-positive CSC population thereby increasing or restoring cisplatin sensitivity.