P1.03-041 Exploitation of the Cancer Stem Cell Marker ALDH1 Within the Vitamin a/Retinoic Acid Axis Promotes Re-Sensitization of Cisplatin Resistant NSCLC

Despite significant advances in personalized medicine in recent decades, cisplatin remains the mainstay chemotherapy in the treatment of NSCLC. The major clinical challenge facing NSCLC today is the development of pan-resistance to platinum agents. Novel drug design, preclinical and clinical trials working toward the approval of new drugs is a lengthy and costly process and in the interim of the drug identification and commercialization research has turned its focus to two avenues of interest; overcoming cisplatin resistance and the repurposing of approved therapeutics with new indications. Cancer stem cells (CSCs) have been hypothesized to be the initiating cells of therapeutic resistance and tumor recurrence. An ALDH1-positive cell subset has been identified as a key CSC subpopulation present within cisplatin resistant NSCLC sublines. ALDH1 is involved in the metabolism of retinol (vitamin A) and the catalytic conversion of retinal to retinoic acid, where retinoic acid induces cell differentiation. All-trans retinoic acid (ATRA) is a well-established chemotherapeutic agent in the treatment of acute promyelocytic leukemia; it induces the terminal differentiation of immature cells. We hypothesize that treatment of the cisplatin resistant NSCLC sublines with retinol or ATRA will deplete the ALDH1-positive population and subsequently increase or restore cisplatin sensitivity.