Conceptualizing the Next Generation of Induced Proximity Strategies for Cancer Therapy
In the dawning days of 2020, just two months before scientific gatherings would suddenly come to a halt, The Mark Foundation for Cancer Research brought together experts in chemical biology, drug development, and cancer biology to envision the currently untapped potential of therapeutic strategies for cancer based on proximity induction. Organized by Dan Nomura, Professor of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology at University of California, Berkeley, and Becky Bish, Senior Scientific Director at The Mark Foundation, this intensive workshop allowed participants to present their own research and concepts, as well as to interact with others working in the field to catalyze new ideas and spark collaborations.
The Advent of Induced Proximity Strategies for Cancer Therapeutics
As the first generation of drugs designed to harness cellular machinery to degrade specific targets make their way to the clinic, there is a growing recognition of the broad potential therapeutic impact of chemically induced proximity – altering biochemical processes with small molecules that bring two biological macromolecules together. For cancer therapeutics, the most hotly pursued application of proximity-inducing drugs is the targeted degradation of oncogenic proteins. Substantial resources have been invested in the development of proteolysis targeting chimeras (PROTACs) and molecular glues, and both industry and academia are working to overcome obstacles in ligand discovery, linker design, E3 ligase selection, and therapeutic optimization. The goal of the workshop was to brainstorm the next generation of induced-proximity based therapeutics, beyond protein degradation.
Seventeen scientists from institutions across the United States and abroad attended the one-day event. They presented a host of very innovative variations on the theme of induced proximity that will potentially lead to game-changing tools for uncovering new biology as well as therapeutics that could modulate intractable drug targets. Five new projects proposed by workshop participants were funded through The Mark Foundation’s ASPIRE grant program, in alignment with the foundation’s commitment to supporting bold initiatives that take on the toughest challenges in cancer research.