AACR Presentation: Potential small-molecule inhibitors of the Tiam1 oncogene product

May 14, 2021
Events, AIMS, Academic Research

At the American Association for Cancer Research Annual Meeting 2021, the abstract for the research program between Case Western Reserve University School of Medicine and the Case Comprehensive Cancer Center, Ursulain College, and Atomwise researchers was selected for a poster presentation. Learn more about the research program and see the presentation below.


Michaela Stamper
Case Western Reserve University

Co-Authors: Claire Fritz, Stephen Valentino, Lynn Ulatowski, Meghana Gupta, Varsha Thakur, Stacey Chung, Christian Laggner, and Danny Manor

Title: Potential small-molecule inhibitors of the Tiam1 oncogene product 

 

Abstract

T-cell lymphoma invasion and metastasis-inducing factor (Tiam)1 is an established proto-oncogene that drives cancer cell migration and metastasis. The correlation between Tiam1 integrity and patient survival, epithelial-mesenchymal transition, and angiogenesis, render it as an important prognostic factor in multiple human malignancies. Tiam1 is a guanine nucleotide exchange factor (GEF) that facilitates the activation of the small GTPase Rac1, thereby controlling cytoskeletal organization, cell polarity, motility, and invasion. In light of the clinical relevance of Tiam1 signaling, we investigated the utility of small molecule inhibitors that target Tiam1 as a therapeutic intervention strategy. We used an in silico computational approach to screen 10 million compounds for candidate drugs that bind to a select patch on Tiam1’s surface. We then identified 13 compounds that inhibit the migration of Tiam1-expressing A549 cells without affecting overall viability. Our studies open the door for a new targeted therapy approach in Tiam1-relevant cancers.

 


Poster Presentation

On-Demand Poster Presentation (click for high-resolution) 

AACR 2021 Poster

 


About AIMS

The AIMS Award program started in 2017, is designed to support promising researchers with resources that will help advance their work. AIMS Awards target research focused on finding solutions for complex human health conditions. To date, Atomwise has funded 7 rounds of AIMS Awards, completing over 100 collaborative projects and accepting over 775 projects into the program.

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