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

• Published in: Advanced drug delivery reviews Vol. 79-80; pp. 222 - 237
• Main Authors: Choi, Stephen Yiu Chuen, Lin, Dong, Gout, Peter W., Collins, Colin C., Xu, Yong, Wang, Yuzhuo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2014
• Subjects: Acidic culture conditions; Acidic tumor microenvironment; Animals; Antineoplastic Agents - pharmacology; Cancer-associated fibroblasts; Cancer–stromal interactions; Cell Culture Techniques; Coculture Techniques; Drug Design; Drug Evaluation, Preclinical - methods; Extracellular matrix; Humans; In Vitro Techniques; Neoplasms - drug therapy; Neoplasms - pathology; Patient-derived xenografts; Regulatory immune cells; Tumor heterogeneity; Tumor Microenvironment - physiology; Xenograft Model Antitumor Assays - methods; Cancer-associated fibroblasts; Acidic tumor microenvironment; Regulatory immune cells; Cancer–stromal interactions; Patient-derived xenografts; Tumor heterogeneity; Extracellular matrix; Acidic culture conditions
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2014.09.009

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. [Display omitted]