Development of In Vitro Co-Culture Model in Anti-Cancer Drug Development Cascade.
BACKGROUND
Tumour microenvironment is recognized as a major determinant of intrinsic resistance to anticancer therapies. In solid tumour types, such as breast cancer, lung cancer and pancreatic cancer, stromal components provide a fibrotic niche, which promotes stemness, EMT, chemo- and radioresistance of tumour. However, this microenvironment is not recapitulated in the conventional cell monoculture or xenografts, hence these in vitro and in vivo preclinical models are unlikely to be predictive of clinical response; which might attribute to the poor predictively of these preclinical drug-screening models.


CONCLUSIONS
In this review, we summarized recently developed co-culture platforms in various tumour types that incorporate different stromal cell types and/or extracellular matrix (ECM), in the context of investigating potential mechanisms of stroma-mediated chemoresistance and evaluating novel agents and combinations. Some of these platforms will have great utility in the assessment of novel drug combinations and mechanistic understanding of the tumor-stroma interactions.
West China School of Medicine, Sichuan University, Chengdu, 610041. China.
Ruiling
R
Xu
Cancer Research UK Cambridge Institute, The University of Cambridge, Cambridge CB2 0RE. United Kingdom.
Frances M
FM
Richards
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018920:Coculture Techniques; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix / Q000187:drug effects; D005818:Genetic Engineering; D057166:High-Throughput Screening Assays; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents
Tumour microenvironment; anti-cancer drug; cancer; co-culture; drug development; tumour-stroma crosstalk