title: Lessons from patient-derived xenografts for better in vitro modeling of human cancer.
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.
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada. Electronic address: schoi@bccrc.ca.
authors.forename: Stephen Yiu Chuen
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada. Electronic address: dlin@bccrc.ca.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC, Canada. Electronic address: pgout@bccrc.ca.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gout
authors.affiliation: Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada. Electronic address: ccollins@prostatecentre.com.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.affiliation: Department of Urology, Second Affiliated Hospital of Tianjin Medical University, Tianjin, P.R. China. Electronic address: xymnwk@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC, Canada; Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Vancouver Prostate Centre, Vancouver, BC, Canada. Electronic address: ywang@bccrc.ca.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D059016:Tumor Microenvironment / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents
keywords: Acidic culture conditions; Acidic tumor microenvironment; Cancer-associated fibroblasts; Cancer–stromal interactions; Extracellular matrix; Patient-derived xenografts; Regulatory immune cells; Tumor heterogeneity