Precision target discovery in high-risk soft tissue sarcoma

Aim/goals:

1. Define the molecular ‘fingerpint’ of high-risk soft tissue sarcomas (STS).
2. To identify the immune landscape of high-risk sarcomas and identify therapeutic sensitivities to immune-based therapies.
3. To understand how the molecular fingerprint of high-risk sarcomas evolves over the course of cancer treatments and recurrence.
4. To develop computational strategies to support precision oncology reports for high-risk sarcomas.

Summary:

Sarcomas are cancers derived from musculoskeletal tissues such as muscle, fat, and bone. These cancers are rare and poorly understood, yet disproportionately represent 10-15% of solid cancers in children and young adults. There are over 60 histologic subtypes soft tissue sarcomas (STS), and majority of these subtypes are not sensitive to, or respond poorly to standard chemotherapies. For these reasons, metastatic STS is a high fatality condition for which there is a paucity of treatment options.

Harnessing advances in genetic and molecular sequencing technologies, our group is characterizing the mutational and molecular profiles of high-risk STS. Using novel computational strategies, we will integrate tumour mutations, gene expression and protein expression to identify key “molecular fingerprints” of high-risk STS. We will collectively analyze a range of high-risk STS looking for shared molecular fingerprints that identify druggable pathways, predict immunotherapy susceptibilities, identify new targets for next generation immunotherapy development, and chart the evolution of these molecular fingerprints with present standard of care treatment. Our goal is to assess how these fingerprints can inform precision oncology initiatives, specifically focusing on those that could encompass multiple STS subtypes. This strategy has the potential to overcome the limitation of rare samples within each sarcoma subtype, and to identify molecular targets that can be translated to a larger group of patients.