Metabolic Stress and the Tumor Ecosystem: New Paradigms for Tumor Progression and Therapy

Cosimo Commisso, PhD
Interim Director and Deputy Director 
NCI-Designated Cancer Center
Professor
Cancer Metabolism and Microenvironment Program
Sanford Burnham Prebys Medical Discovery Institute
La Jolla, CA, USA

The host of this conference is Dr. Jean-François Côté, President and Scientific Director of the IRCM and Director of the Cytoskeletal Organization and Cell Migration Research Unit. 

This event will be held at the IRCM and on Zoom (ID: 914 2700 2500 – Code: 203772).

About this conference
I will be presenting on how metabolic stress influences tumor progression and therapy, with a focus on glutamine metabolism in pancreatic cancer. My lab’s work demonstrates that glutamine depletion triggers epithelial-mesenchymal transition (EMT), regulated by the master transcription factor Slug through MEK/ERK and ATF4 signaling, driving metastasis. We explored the therapeutic potential of the glutamine antagonist DON, showing its ability to suppress tumor growth and metastasis by targeting metabolic adaptations like asparagine synthetase (ASNS) upregulation. Additionally, our research uncovered the role of macropinocytosis, regulated by cell polarity proteins and aPKCs, in nutrient acquisition under glutamine stress. By combining DON with inhibitors of these pathways, we observed enhanced anti-tumor effects. This work highlights how understanding tumor metabolic adaptations can guide innovative therapeutic strategies to combat cancer progression and metastasis.

About Cosimo Commisso
Dr. Commisso obtained his Ph.D. at the University of Toronto in the Department of Molecular Genetics and completed his postdoctoral training at New York University School of Medicine. He made the seminal discovery that Ras-mutant cancer cells use macropinocytosis as an amino acid supply pathway. Dr. Commisso is currently a Professor and Interim Director of the NCI-designated Cancer Center at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California. His laboratory’s research interests are centered on elucidating the underlying mechanisms of how metabolic stress influences the tumor ecosystem in pancreatic cancer. The lab is particularly interested in identifying metabolic adaptations and dependencies that contribute to tumor progression and can be targeted to develop novel therapeutic modalities for this disease.

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