In recent years, immune checkpoint blockade (ICB) has provided oncologists with a powerful new tool. But while ICB has been found to be effective in microsatellite instability-high (MSI-H) colorectal cancer, it is far less effective in microsatellite stable (MSS) colorectal cancer. We have developed glycogen synthase kinase-beta (GSK-3-b) inhibitors that are effective in cases of MSS colorectal cancer.
Globally, among cancers, colorectal cancer ranks third in terms of incidence and second in terms of mortality. Treatment options include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. ICB, developed in recent years, has been found to be effective in MSI-H colorectal cancer, but not in MSS colorectal cancer. Thus, there remains a need for treatment for the ~85 % of patients with MSS for whom ICB is not effective.
Innovation and Meaningful Advantages
We have demonstrated that inhibition of GSK3-b with the small molecule 9-ING-41 stimulates natural killer and T cell activity, reduces vascular endothelial growth factor levels, and induces colon cancer cell death. The immune modulatory effects of GSK3-b could also attenuate or block COVID-19 in patients with early or less severe infection.
We are interested in exploring 1) startup opportunities with investors; 2) research collaborations with leading pharmaceutical companies to develop this method of treatment; and 3) licensing opportunities with companies.
Wafik El-Deiry, MD, PhD
Mencoff Family University Professor of Medical Science
Professor of Pathology and Laboratory Medicine
Brown Tech ID 3107
Vanderwalde AM, Darabi S, Korn WM, Mazar AP, Giles FJ, Crawford L, Safran H, El-Deiry WS, and Carneiro BA. The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer. Molecular Cancer Therapeutics. 2021 Jan;20(1): doi: 10.1158/1535-7163.MCT-20-0497.
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