In with the old! Repurposing disulfiram to target cancer stem cells (CSCs) and the root of cisplatin resistance

Cisplatin remains the cornerstone of NSCLC management. Despite initial sensitivity tumours develop resistance, undermining the cytotoxic effect of cisplatin. Numerous mechanisms have been investigated in terms of cisplatin resistance and its development, however, the clinical issue of resistance remains. An avenue of interest is the CSC hypothesis, in which the survival and expansion of highly resistant CSCs during chemotherapy are thought to be a contributing factor of resistance. Specific inhibition of key CSC markers in combination with chemotherapy may subvert the inherent resistance of the CSCs thereby restoring therapeutic effeciency. One such CSC marker is aldehyde dehydrogenase 1 (ALDH1). We hypothesise that inhibition of the ALDH1-positive CSCs within cispaltin resistant NSCLC will resensitise the cells to cisplatin.