Characterizing the molecular and clinical landscape of BRAF mutant colorectal cancer: toward the identification of novel therapeutic vulnerabilities
BRAF is a common oncogene in cancer and while today’s technologies have led to the development of effective therapies for certain BRAF mutations, a large subset of tumours with these mutations remains unresponsive to treatment. Ten per cent of colorectal cancers have a BRAF mutation and are often associated with poor outcomes when compared to colorectal cancers without BRAF mutations. Our preliminary research shows differences in the mutational landscape and gene expression patterns between V600 BRAF mutant colorectal cancers and the non-V600 mutant tumours which are less well characterized. Presently there are targeted treatments available for colorectal cancers with BRAF V600 mutation but there are no established targeted treatments for colorectal cancers with non-V600 BRAF mutations.
This data science project investigates the commonalities and differences between these subtypes of colorectal cancers in relation to acquired or intrinsic resistance to therapies. We will employ bulk RNA sequencing methods from publicly available colorectal tumour data sets and on patient derived tumours grown in mice from the BEAVER trial. Using colorectal tumour tissue samples from another cohort, we will validate the findings from the RNA sequencing analyses and investigate the cell populations within these tumours using multiplex immunofluorescence technologies. This large cohort of V600 and non-V600 BRAF mutant colorectal tumours will allow us to uncover potential biomarkers of treatment response to personalize patient care. This could dramatically improve the efficacy of treatments that are provided to patients with BRAF mutant colorectal cancers that are resistant to standard targeted therapies.
Quotes
“I have always been driven to cancer research due to personal experiences I’ve had with family members affected by cancer. Being recognized for my hard work and receiving this award means so much to me as it will allow me to take my research to new heights. I am extremely excited about continuing this research with the support of Marathon of Hope and the Terry Fox Research Institute to better the lives of cancer patients.” – Emmanuelle Rousselle, HI&DS Award Recipient
“Metastatic colorectal cancers frequently harbor BRAF mutations, making them very aggressive and hard to treat. While treatments are available for V600 BRAF mutations, nonV600 BRAF mutations, more prevalent in younger patients with early onset colorectal cancer, lack targeted therapies. Emma's project will explore the unique characteristics of BRAF mutant colorectal cancers at the DNA, RNA, and protein level. She hopes to discover new therapeutic vulnerabilities to improve treatment outcomes for patients with these hard-to-treat cancers.” – Drs. Gerald Batist and April Rose, mentors