MEK is a promising target in the basal subtype of bladder cancer
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Nathan M. Merrill1,2, Nathalie M. Vandecan1,2, Kathleen C. Day5, Phillip L. Palmbos1,2, Mark L. Day5, Aaron M. Udager2,4, Sofia D. Merajver1,2 and Matthew B. Soellner1,2,3
1 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
2 University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA
3 Department of Chemistry, University of Michigan, Ann Arbor, MI, USA
4 Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA
5 Department of Urology, University of Michigan, Ann Arbor, MI, USA
|Matthew B. Soellner,||email:||[email protected]|
|Sofia D. Merajver,||email:||[email protected]|
Keywords: bladder cancer; drug screen; 3D culture; basal bladder cancer; MEK inhibition
Received: June 13, 2020 Accepted: September 24, 2020 Published: November 03, 2020
While many resources exist for the drug screening of bladder cancer cell lines in 2D culture, it is widely recognized that screening in 3D culture is more representative of in vivo response. Importantly, signaling changes between 2D and 3D culture can result in changes to drug response. To address the need for 3D drug screening of bladder cancer cell lines, we screened 17 bladder cancer cell lines using a library of 652 investigational small-molecules and 3 clinically relevant drug combinations in 3D cell culture. Our goal was to identify compounds and classes of compounds with efficacy in bladder cancer. Utilizing established genomic and transcriptomic data for these bladder cancer cell lines, we correlated the genomic molecular parameters with drug response, to identify potentially novel groups of tumors that are vulnerable to specific drugs or classes of drugs. Importantly, we demonstrate that MEK inhibitors are a promising targeted therapy for the basal subtype of bladder cancer, and our data indicate that drug screening of 3D cultures provides an important resource for hypothesis generation.
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