December 17, 2020

Five Grants Awarded to Accelerate a New Class of Cancer Drugs Based on Induced Proximity

NEW YORK – The Mark Foundation for Cancer Research (MFCR) has awarded five new grants in support of an important, emerging approach to cancer therapeutics. The projects are centered around the molecular strategy of induced proximity, which involves controlling the physical distance between proteins to regulate or perturb biological processes in the cancer cell.

One of the biggest challenges in developing new cancer therapies is that many proteins are not tractable to the traditional approach in drug discovery of directly inhibiting the function of a therapeutic target. The induced proximity model aims to overcome this hurdle by altering the target protein’s function without requiring that small molecules be direct inhibitors.

Substantial efforts are already under way to design drugs that harness cellular machinery for the degradation of specific targets, a strategy known as targeted protein degradation (TPD). These drugs, which include proteolysis-targeting chimeras (PROTACs) and molecular glue degraders, use bifunctional small molecules to connect target proteins with cellular modifiers that lead to their breakdown within the cell. More recent advances in induced proximity include methods that result in apoptosis, phosphorylation, and epigenetic modulation, all of which are promising avenues for cancer therapy.

In January 2020, MFCR brought together experts in chemical biology, drug discovery, and cancer biology in a workshop to envision new strategies for cancer therapeutics based on induced proximity. The workshop, organized by Daniel Nomura, PhD, from University of California, Berkeley, and Becky Bish, PhD, from MFCR, was attended by scientists from the United States and abroad who brainstormed new and innovative approaches within this therapeutic category. Attendees represented academic institutions as well as biotechnology companies.

Today, MFCR is announcing that it has awarded four grants that arose from the January meeting, as well as one additional grant. All five projects are designed to support high-risk, high-reward research that addresses key feasibility and proof-of-concept questions.

The following ASPIRE awards were selected in a competitive request for proposals that followed the January meeting:

An additional induced proximity project was selected for MFCR’s new Drug Discovery Partnership program, which is designed to accelerate the trajectory of promising scientific discoveries towards becoming therapeutics that will benefit cancer patients.

  • Craig Crews, PhD, is leading a team at Yale School of Medicine to continue developing a TPD approach for treating chordoma, a rare cancer of the spine and skull base. The foundation for this work in the Crews lab originated in a successfully completed study funded by a Therapeutic Innovation Award jointly granted by MFCR and the Chordoma Foundation in 2018.

“At The Mark Foundation, we are always excited to learn how the most innovative thinkers are applying the latest technology advances to tackling challenges in cancer,” said Michele Cleary, PhD, MFCR CEO. “The recipients of these awards demonstrate the type of out-of-the-box problem solving that we believe will translate to new therapies and tools that can substantially move the field of cancer research forward.”

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