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Actuate Therapeutics Launches Strategic Research Initiative to Combine Elraglusib with RAS Inhibitors
Inform future clinical development plans, further establishing elraglusib as a potential backbone therapy in difficult-to-treat cancersMechanisms of action
About this update from Actuate Therapeutics, Inc.
[{"type":"text","content":"Inform future clinical development plans, further establishing elraglusib as a potential backbone therapy in difficult-to-treat cancersMechanisms of action support enhanced activity of GSK-3β plus RAS inhibitionPreclinical combination results expected in 2H2026 CHICAGO and FORT WORTH, Texas, March 09, 2026 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), today announced the launch of an expanded research initiative evaluating combinations of its clinical-stage GSK-3β inhibitor elraglusib with emerging RAS-targeted therapies. Despite recent advances in RAS-targeted therapies, adaptive resistance mechanisms and pathway reactivation remain some of the key barriers to achieving durable responses in patients (Dilly et al., Cancer Discov 2024). Based on the mechanisms of action, GSK-3 inhibition may represent a critical complementary strategy capable of enhancing RAS-targeted therapies by suppressing downstream survival signaling and resistance pathways, including NF-κB–mediated survival signalingMYC-driven transcriptional programsmetabolic adaptation and oxidative stress bufferingtumor microenvironment immune suppression In addition, RAS-mutant tumors — particularly pancreatic cancer — are widely considered immunologically resistant. Preclinical research suggests that GSK-3β inhibition may enhance antigen presentation, activate T cells and NK cells, and reduce exhausted T-cells. By simultaneously targeting tumor intrinsic survival pathways and modulating the tumor immune microenvironment, the combination of elraglusib and RAS inhibitors has the potential to create a multi-modal therapeutic strategy designed to overcome resistance and expand clinical benefit in RAS-driven cancers. Expanding the Strategic Opportunity for Elraglusib Elraglusib is a best-in-class, highly selective GSK-3β inhibitor with broad potential across multiple oncology indications, including pancreatic cancer, melanoma, colorectal cancer, and sarcoma. The investigational product has been administered to more than 500 patients and is currently being evaluated in a Phase 2 trial in metastatic pancreatic cancer (mPDAC). The ...