Oncotarget

Research Papers:

MEK is a promising target in the basal subtype of bladder cancer

Nathan M. Merrill, Nathalie M. Vandecan, Kathleen C. Day, Phillip L. Palmbos, Mark L. Day, Aaron M. Udager, Sofia D. Merajver _ and Matthew B. Soellner _

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Oncotarget. 2020; 11:3921-3932. https://doi.org/10.18632/oncotarget.27767

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Abstract

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

Correspondence to:

Matthew B. Soellner,email: soellner@umich.edu
Sofia D. Merajver,email: smerajve@med.umich.edu

Keywords: bladder cancer; drug screen; 3D culture; basal bladder cancer; MEK inhibition

Received: June 13, 2020     Accepted: September 24, 2020     Published: November 03, 2020

Copyright: © 2020 Merrill et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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