Three‐dimensional culture models to study drug resistance in breast cancer

Abstract

Despite recent advances in breast cancer treatment, drug resistance frequently presents as a challenge, contributing to a higher risk of relapse and decreased overall survival rate. It is now generally recognized that the extracellular matrix and cellular heterogeneity of the tumor microenvironment influences the cancer cells' ultimate fate. Therefore, strategies employed to examine mechanisms of drug resistance must take microenvironmental influences, as well as genetic mutations, into account. This review discusses three‐dimensional (3D) in vitro model systems which incorporate microenvironmental influences to study mechanisms of drug resistance in breast cancer. These bioengineered models include spheroid‐based models, biomaterial‐based models such as polymeric scaffolds and hydrogels, and microfluidic chip‐based models. The advantages of these model systems over traditionally studied two‐dimensional tissue culture polystyrene are examined. Additionally, the applicability of such 3D models for studying the impact of tumor microenvironment signals on drug response and/or resistance is discussed. Finally, the potential of such models for use in the development of strategies to combat drug resistance and determine the most promising treatment regimen is explored.

The biomimetic extracellular matrix: a therapeutic tool for breast cancer research

“…In fact, these hydrogels were used in the presence of BC 3D modeling systems to improve the growth of spheroidal cultures, which resemble tumor conditions in vivo 57 . This platform can be used to study the synergy between fibroblasts and cancer cells and has also been considered a good tool for drug dissemination 58 . Interestingly, the sensitivity of MDA-MB-231BCCsembedded in Matrigel® gels in response to the drug doxorubicin (DOX) was significantly higher compared to single-layer 2D cells 59 .…”

Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models

“…Increasing in model complexity is our ex vivo tumor model of MDTs that not only offers a 3D structure, but also includes mouse-infiltrating stromal cells which may impact the tumor response to a therapeutic agent. In vivo models further increase model complexity by incorporating important elements such as drug metabolism, influence of endogenous hormones and mammalian physiology 39 . In general, our study suggests that the relative carboplatin response of our 3D models was in line with in vivo results.…”

Alzheimer’s Disease, and Breast and Prostate Cancer Research: Translational Failures and the Importance to Monitor Outputs and Impact of Funded Research

“…Three-dimensional (3-D) tumor spheroids have been shown to more closely resemble the complexity of tumor tissue architecture and biology, and can be used to perform drug screening in vitro [29]. For instance, such models have been used to study drug resistance [195], drug response, and diffusion [196] in BC. Along the same line, 3-D models of PC, integrated in high-throughput testing platforms [197,198], are speeding up the drug screening process, and may prove useful tools for personalized medicine, while reducing costs and time [199].…”