Systems approaches to uncovering the contribution of environment-mediated drug resistance

Curr Opin Solid State Mater Sci. 2022 Oct;26(5):101005. doi: 10.1016/j.cossms.2022.101005. Epub 2022 May 13.


Cancer drug response is heavily influenced by the extracellular matrix (ECM) environment. Despite a clear appreciation that the ECM influences cancer drug response and progression, a unified view of how, where, and when environment-mediated drug resistance contributes to cancer progression has not coalesced. Here, we survey some specific ways in which the ECM contributes to cancer resistance with a focus on how materials development can coincide with systems biology approaches to better understand and perturb this contribution. We argue that part of the reason that environment-mediated resistance remains a perplexing problem is our lack of a wholistic view of the entire range of environments and their impacts on cell behavior. We cover a series of recent experimental and computational tools that will aid exploration of ECM reactions space, and how they might be synergistically integrated.

Keywords: ECM; cell signaling; drug resistance; tensor decomposition.