Evaluation of chemotherapeutics in a three-dimensional breast cancer model

Journal of Cancer Research and Clinical Oncology
Carrie J LovittVicky M Avery

Abstract

Utilization of miniaturized three-dimensional (3D) cell culture-based assays enables investigation into the anticancer activity of drug candidates and further elucidation of the anticancer profile of standard-of-care chemotherapeutic agents against tumor cells. Drug discovery assays established using 3D cell culture, which better recapitulate the tumor microenvironment, may more accurately reflect the antitumor activity of compounds. Several standard-of-care anticancer drugs, epirubicin, paclitaxel and vinorelbine, were evaluated against a panel of breast cancer cell lines grown in a 3D cell culture microenvironment in the presence of extracellular matrix. A comparison of this antitumor activity in 3D conditions was made with that observed in traditional two-dimensional (2D) monolayer conditions. Examination of the above mentioned drugs against breast tumor cells cultured in 3D conditions demonstrated significantly altered potency and efficacy in comparison with cells propagated in a 2D monolayer system. The differences observed were cell line-dependent and drug-specific; the triple-negative cell line MDA-MB-231 and the endocrine receptor-positive cell line MCF-7 consistently displayed resistance to therapeutics with distinct m...Continue Reading

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