REC-4881

Combined treatment with the MEK inhibitor TAK-733 and immune checkpoint inhibitors was proposed as a promising therapeutic strategy for this subgroup. This novel VM-based molecular subtyping system for MIBC shows strong potential for clinical application in prognosis prediction, immunotherapy response evaluation, and targeted drug discovery, providing a framework to guide personalized treatment strategies for MIBC patients.

P1/2, N=67, Recruiting, Recursion Pharmaceuticals Inc. | Trial completion date: Jul 2026 --> Sep 2027 | Trial primary completion date: Jul 2026 --> Jun 2027

P2, N=18, Terminated, Recursion Pharmaceuticals Inc. | N=60 --> 18 | Trial completion date: Jan 2027 --> Feb 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Feb 2025; Study was terminated due to sponsor decision. This decision was not related to safety concerns.

We identified 100 total drug hits and found that STAG2 KO sensitized cells to treatment with PLK1 inhibitor rigosertib, whereas STAG2 KO protected cells from treatment with MEK inhibitor TAK-733 and PI3K inhibitor PI-103. Finally, synergy experiments revealed that berzosertib exhibits significant synergistic cytotoxicity in combination with cisplatin against MIBC cells. Altogether, our study presents evidence that berzosertib, PI-103, and the combination of berzosertib with cisplatin may be novel opportunities to investigate as precision medicine approaches for MIBC patients based on STAG2 tumor expression.

This work created a 12-gene signature based on NM, preliminary investigated immune infiltration in two risk categories, and discovered some possible anti-tumor medications. To sum up, our study findings offer fresh perspectives on the roles played by NM-associated genes in HCC development, prognosis, immunological response, and medication screening.

P2, N=60, Active, not recruiting, Recursion Pharmaceuticals Inc. | Recruiting --> Active, not recruiting

P2, N=60, Recruiting, Recursion Pharmaceuticals Inc. | Not yet recruiting --> Recruiting

P2, N=60, Not yet recruiting, Recursion Pharmaceuticals Inc. | Initiation date: Oct 2023 --> Jan 2024

P1/2, N=73, Recruiting, Recursion Pharmaceuticals Inc. | Phase classification: P2 --> P1/2 | N=37 --> 73

High CLIC1 expression samples were more sensitive to camptothecin, cisplatin, doxorubicin, erlotinib, paclitaxel, rapamycin, clofarabine, tanespimycin, methotrexate, everolimus, TAK-733, trametinib and AZD8330. Single-cell analysis unveiled that CLIC1 was expressed ubiquitously in tumor cells and tumor microenvironment. Overall, CLIC1 was a promising treatment vulnerability in glioma.

P2, N=37, Recruiting, Recursion Pharmaceuticals Inc. | N=94 --> 37

P2, N=60, Not yet recruiting, Recursion Pharmaceuticals Inc.