期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 79-80, 期 -, 页码 222-237出版社
ELSEVIER
DOI: 10.1016/j.addr.2014.09.009
关键词
Patient-derived xenografts; Acidic tumor microenvironment; Cancer-stromal interactions; Extracellular matrix; Tumor heterogeneity; Cancer-associated fibroblasts; Regulatory immune cells; Acidic culture conditions
资金
- Canadian Institutes of Health Research [IPR-119991, MOP-123449]
- Terry Fox Research Institute
- BC Cancer Foundation
- Prostate Cancer Canada
- Tianjin Thousand Talents Program
- CIHR Frederick Banting and Charles Best Master's Award
- CIHR Doctoral Award
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. (C) 2014 The Authors. Published by Elsevier B.V.
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