Elsevier

Advanced Drug Delivery Reviews

Volumes 79–80, 15 December 2014, Pages 222-237
Advanced Drug Delivery Reviews

Lessons from patient-derived xenografts for better in vitro modeling of human cancer,☆☆

https://doi.org/10.1016/j.addr.2014.09.009Get rights and content
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open access

Abstract

The development of novel cancer therapeutics is often plagued by discrepancies between drug efficacies obtained in preclinical studies and outcomes of clinical trials. The inconsistencies can be attributed to a lack of clinical relevance of the cancer models used for drug testing. While commonly used in vitro culture systems are advantageous for addressing specific experimental questions, they are often gross, fidelity-lacking simplifications that largely ignore the heterogeneity of cancers as well as the complexity of the tumor microenvironment. Factors such as tumor architecture, interactions among cancer cells and between cancer and stromal cells, and an acidic tumor microenvironment are critical characteristics observed in patient-derived cancer xenograft models and in the clinic. By mimicking these crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic.

Keywords

Patient-derived xenografts
Acidic tumor microenvironment
Cancer–stromal interactions
Extracellular matrix
Tumor heterogeneity
Cancer-associated fibroblasts
Regulatory immune cells
Acidic culture conditions

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This review is part of the Advanced Drug Delivery Reviews theme issue on “Engineering of Tumor Microenvironments”.

☆☆

Grant support: This study was supported in part by the Canadian Institutes of Health Research (YZW) (IPR-119991 and MOP-123449), Terry Fox Research Institute (YZW), BC Cancer Foundation (YZW), and Prostate Cancer Canada (CCC, YZW). YZW is a recipient of an award from the Tianjin Thousand Talents Program. SYCC is a recipient of a CIHR Frederick Banting and Charles Best Master's Award and a CIHR Doctoral Award.

1

The authors contributed equally to this work.