PhotoStem aims to develop a cutting-edge approach to overcome the main cause of patient relapse in cancer treatment. Cancer stem cells (CSCs) are a small population of cells within a tumour characterised by their ability to self-renew and to induce tumourigenesis. Current chemotherapy acts only on the bulk of the tumour mass, leaving CSCs unaffected; this is thought to be the main cause of resistance to cancer treatment. Despite growing knowledge on the existence of CSCs, similarities to normal stem cells challenges the design of selective inhibitors and modulators. Relapse to cancer treatment is an enormous challenge and there is an urge to identify novel therapeutic approaches to target CSCs.
Photopharmacology is an emerging field that seeks to precisely control the activity of bioactive molecules with light, allowing for activation or repression of biological function at a specific space and time. It constitutes a truly disruptive innovation that can represent a new direction in drug therapy. We herein propose to use novel photoactivable molecules to target CSCs with precise spatiotemporal control using light. Initially, we will develop novel photoswitchable versions of known inhibitors, and will study their effect in leukemia stem cells both in vitro and in zebrafish models. We will then expand our learnings to target CSCs of solid tumours.
The achievement of such an ambitious objective will only be possible via a network of multidisciplinary researchers. The researcher will combine her expertise in drug discovery and leukemia with state-of-the-art photopharmacology techniques from leaders in the field at the host institution. Training-through-research at the partner organisations that include well-recognised experts in haematological malignancies, myeloid zebrafish models and CSC xenograft models will enable the expansion to in vivo applications. The proposed work will provide both new directions in targeted cancer therapy and powerful tools for cell biology.