The Mark Foundation for Cancer Research has awarded five grants to support research of induced proximity, which involves controlling the physical distance between proteins to regulate or perturb biological processes in the cancer cell.
The following ASPIRE awards were selected in a competitive request for proposals that followed the January MFCR meeting:
Amit Choudhary and his team from Harvard Medical School are exploring whether small molecules called phosphorylation-inducing chimeric small molecules, which bring kinases into close proximity with target proteins, can enhance phosphorylation in cancer targets. The ultimate goal is to use aberrant phosphorylation to evoke an immune response.
Arvin Dar and his lab at the Icahn School of Medicine at Mount Sinai have developed a compound dubbed trametiglue, a version of the FDA-approved MEK inhibitor trametinib, that has enhanced interfacial binding properties. These improved properties show promise in overcoming the resistance that’s commonly seen with trametinib. Trametiglue and its analogs are being used as research tools and studied as potential leads for new therapeutics.
H. Courtney Hodges of the Baylor College of Medicine, and Nate Hathaway, of the University of North Carolina, are collaborating to develop bifunctional small molecules that can activate SWI/SNF-dependent transcriptional enhancers. SWI/SNF is an important chromatin remodeling complex that can lead to cancer when inactivated.
Benjamin Stanton of Nationwide Children’s Hospital and The Ohio State University College of Medicine, and his collaborator Jun Qi, of Dana-Farber Cancer Institute, are developing induced proximity-based precision therapeutics for rhabdomyosarcoma that result in the degradation of the drivers of oncogenic transcriptional programs in this rare pediatric solid tumor.
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 is leading a team at Yale School of Medicine to continue developing a TPD approach for treating chordoma. 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.