Research
Major Research Themes
Clinical trials to test novel MAPK inhibitor combinations in patients with non-V600 BRAF mutant cancer
Defining mechanisms of resistance to MAPK inhibitors in cancers with non-V600 BRAF mutations
Evaluating the role of mutant NRAS in mediating immunotherapy resistance in melanoma
Characterizing predictors of therapeutic response and resistance in genitourinary cancers
Introduction to the MAPK pathway
BRAF is a serine threonine kinase that signals via the Mitogen Activated Protein Kinase Pathway. BRAF is one of the most frequently mutated oncogenes in cancer. The most common type of BRAF mutations are called BRAF V600 or Class 1 BRAF mutations. However, approximately 1/3 of all oncogenic mutations are non-V600 mutations, which can be classified as Class 2 or Class 3 BRAF mutations according to defined molecular characteristics. There are very effective targeted therapies (MAPK pathway inhibitors) that prolong survival and cure rates for patients with Class 1 BRAF mutant tumors. But unfortunately these same MAPK inhibitors are less effective against Class 2 & 3 BRAF mutant tumors. Our research focusses on these Class 2 and 3 BRAF mutations. Our goal is to develop novel therapeutic strategies that can be used to treat tumors that are driven by Class 2 & 3 BRAF mutations
NRAS signaling pathway
NRAS is a GTPase and a protooncogene that is mutated and constitutively activated in 20-30% of metastatic melanomas. Currently, the only effective therapies for patients with NRAS mutant metastatic melanoma are immune checkpoint inhibitors. Patients with NRAS mutations are less likely to benefit from immune checkpoint inhibitors compared to patients with NRAS wildtype melanoma. We are using cancer cell lines, syngeneic mouse models and analyses of human melanoma tumors to try to figure out why NRAS mutant melanomas are more resistant to immune checkpoint inhibitors. We hope that our research will lead to new, effective treatments for patients with NRAS mutant melanoma.
Metastatic Castration‑Resistant Prostate Cancer:
Mechanisms of Resistance and Precision Therapeutics
Metastatic castration‑resistant prostate cancer (mCRPC) develops when tumors acquire the ability to sustain androgen receptor (AR) signaling despite androgen‑deprivation therapy. Our research program combines patient‑derived liquid biopsies with fundamental molecular studies to understand how AR‑driven and AR‑independent resistance mechanisms emerge, evolve, and shape therapeutic outcomes.
Using circulating tumor DNA (ctDNA) and other liquid biopsy platforms, we track the real‑time evolution of AR locus alterations, including amplifications, enhancer duplications, structural rearrangements, and splice variants. These clinical datasets are integrated with mechanistic studies in cellular and organoid models to delineate the signaling pathways that enable tumors to bypass AR blockade, activate compensatory survival programs, or transition toward lineage plasticity.
By bridging patient‑centered molecular profiling with experimental dissection of resistance pathways, this project aims to identify actionable vulnerabilities and guide the development of next‑generation therapeutic strategies for advanced prostate cancer. Ultimately, our goal is to translate molecular insights into more precise, durable treatments for patients with mCRPC.
The LUMIÈRE liquid biopsy group was established in 2023 by a group of clinician-scientists and scientists who were collectively interested in implementing liquid biopsy testing as part of cancer care and in cancer research. The consortium, led by Dr. April Rose, is based at the Jewish General Hospital in collaboration with Dr. Adriana Aguilar, Dr. Mark Basik, Dr. Gerald Batist, Dr. Melica N. Brodeur, Dr. Nathalie Johnson, Dr. Andreas Papadakis, and Dr. Alan Spatz. The McGill Centre for Translational Research in Cancer and OptiLab are central collaborative entities of LUMIÈRE.
LUMIÈRE’s mission is to develop an expertise and to be a center of excellence for liquid biopsy testing in cancer research and cancer care. This covers a large spectrum of liquid biopsy applications and indications, including initial diagnostic molecular profiling, minimal residual disease monitoring, molecular profiling at recurrence and optimizing personalized therapy
The work done within our consortium would not be possible without the support of our funders including AstraZeneca, Pfizer, Teamsters Canada, illumina, and Marathon of Hope Cancer Centres Network and the McGill Center for Translational Cancer Research.
READ MORE ABOUT LUMIERE CURRENT PROJECTS
Research Funding
