2023 Research Update from the Gladdy Lab at Princess Margaret Cancer Centre 

Project 1 - Genetic Landscape of Adult RMS

Rhabdomyosarcoma (RMS) is a tumor of the skeletal muscle that most commonly affects young adults. Although it is the most common pediatric soft tissue sarcoma, it generally has a worse prognosis in adults.

With the support of the James J. Hammond Fund, Dr. Rebecca Gladdy and her collaborators are studying the genetic signatures in adult RMS to better understand how they differ than those of pediatric patients. This work will also help generate sophisticated cancer models to validate genetic changes in RMS and develop more precise and effective treatments for adult patients. By gaining a better understanding of how adult RMS behaves, Dr. Gladdy hopes to discover personalized therapies to ultimately, improve outcomes for all patients.

Over the last year, Dr. Rebecca Gladdy and her team have continued collecting genomic samples from new patients, and have also leveraged data from the Canadian Sarcoma Research and Clinical Collaboration database. With this valuable information, the team has identified several genomic alterations varied by subtype and are well on their way to establishing a comprehensive molecular and genomic profile of adult RMS. The next stage is to explore the epigenetic landscape of the genomic data to better assess how tumour cells are modified and regulated. This comprehensive approach will allow the team to understand the correlation between genetic and epigenetic factors in RMS, and potentially identify novel therapies.

Project 2 - Magnetic Resonance-Guided High Intensity Focused Ultrasound (MRgHIFU) as Novel Therapy for Advanced RMS

Immunotherapies are treatments that prompt the immune system to find and destroy

cancer cells and are a less toxic intervention than conventional chemotherapy. However, tumours like RMS have yet to be successfully treated by immunotherapy.

Dr. Gladdy is hoping to change this by pursuing a multimodal treatment approach using Magnetic Resonance-Guided High Intensity Focused Ultrasound (MRgHIFU), which generates mild hyperthermia in a tumour site. This process should release a heat sensitive chemotherapeutic agent locally to reduce the size of the tumour, while limiting toxicity and side effects. In addition, stimulating mild hyperthermia may activate the immune system to identify cancer cells, and fight back.

To validate MRgHIFU as a viable treatment for RMS, Dr. Gladdy and her collaborators are testing its effectiveness on reducing tumour growth and improving survivorship. The team is also continuing to profile treated tumors to determine if this method prompts a significant immune response and, in turn, improves treatment efficacy. Ultimately, thanks to the support of the James J. Hammond Fund, the Gladdy Lab is pursuing cutting-edge research to transform care and outcomes for patients with RMS.