Grant: CIHR - ICR / Cancer Research Society Partnership - Research Grants

Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in Canadian children. RMS is a skeletal muscle-derived soft-tissue sarcoma affecting children and adolescents. Management of RMS is challenging and the cure rate for metastatic RMS remains below 30% thus underscoring the need for new treatments. To do so, we need to further identify and understand the dysregulated mechanisms that contribute to RMS, as well as how these can be targeted for therapeutic benefit. Our research team recently showed that the amount of pannexin 1 (PANX1) is very low in RMS when compared to normal skeletal muscle. Notably, increasing PANX1 protein levels in RMS significantly reduced tumour progression, indicating that augmenting PANX1 levels would be clinically beneficial for RMS. In this proposal, we will 1) investigate the role that PANX1 down-regulation plays in RMS development and progression, 2) decipher the molecular pathways by which increasing PANX1 levels alleviates RMS malignant properties. Together with our previous work, results from these proposed studies will bring new knowledge related to the mechanisms involved in RMS pathogenesis, as well as insights on the key pathways by which increasing PANX1 levels halts RMS progression, which are both critical to design better therapeutic approaches for patients with RMS.