The Canadian Cholangiocarcinoma Collaborative (C3) Whole Genome Transcriptome Sequencing Project

Project aims/goals

  • To enrol participants into the Canadian Cholangiocarcinoma Collaborative (C3) National Patient Registry and include Whole Genome Transcriptome Sequencing (WGTS) data to help with clinical trial matching and generate Real World Evidence for novel molecular therapy drug submissions
  • To analyse WGTS results alongside matched multiomic data from the C3 to identify novel neoepitopes and tumour associated antigens to generate new immunotherapies and/or enhance tumour infiltrating lymphocyte therapies
  • To increase the number of biliary tract cancer cases within the Marathon of Hope Gold cohort

Summary

The Challenge: Biliary tract cancers (BTC) are rare (~1,000 new cases in Canada per year). When localized, surgical resection is possible, but most patients present with Stage IV disease, where the estimated 5-year survival is <2%. Current systemic chemotherapy offers modest prolongation of survival but at a huge cost to quality of life. Clinical trials of molecularly targeted therapies are reporting a longer and better life for patients with BTC, and prolonged remission has been seen with novel immunotherapies. The promise of emerging BTC research including molecular and immunotherapies offer hope for a durable and long-term survival.

Our Solution: We propose that by integrating comprehensive research into clinical care, at the earliest time possible in a patient's cancer treatment trajectory, we will be able to offer patients access to novel therapies through clinical trials, better appreciate the needs, values, and hopes of Canadian BTC patients and understand the unique challenges in the clinical and research landscape. To accomplish this, we have created the Canadian Cholangiocarcinoma Collaborative (C3), a partnership among patients, caregivers, oncologists and researchers. Our goal is to enhance access to clinical trials and personalized treatments for BTC patients and enable the development of a high-quality immunotherapy pipeline for research and discovery. Importantly, we want to understand the molecular underpinnings of this disease through whole genome transcriptome sequencing so that we can advance novel therapies like Tumour Infiltrating Lymphocyte (TIL) therapy into clinical trials. Through these research opportunities, the C3 will provide much needed hope to affected individuals including patients and families.

Anticipated outcomes and impact

We anticipate identifying and reporting many actionable mutations to participants in our study, as approximately 40-50% of all biliary tract cancers harbor actionable mutations. Beyond known targets, there is also significant potential in the less explored regions of the genome, where we hope to discover novel therapeutic opportunities. Finally, the data generated through this project will contribute to real-world evidence efforts, helping to attract more pharmaceutical companies to Canada and support future drug review submissions.

 

Key Researchers