Abstract
Patient-derived xenograft (PDX) models are used as powerful tools for understanding cancer biology in PDX clinical trials and co-clinical trials. In this systematic review, we focus on PDX clinical trials or co-clinical trials for drug development in solid tumors and summarize the utility of PDX models in the development of anti-cancer drugs, as well as the challenges involved in this approach, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Recently, the assessment of drug efficacy by PDX clinical and co-clinical trials has become an important method. PDX clinical trials can be used for the development of anti-cancer drugs before clinical trials, with their efficacy assessed by the modified response evaluation criteria in solid tumors (mRECIST). A few dozen cases of PDX models have completed enrollment, and the efficacy of the drugs is assessed by 1 × 1 × 1 or 3 × 1 × 1 approaches in the PDX clinical trials. Furthermore, co-clinical trials can be used for personalized care or precision medicine with the evaluation of a new drug or a novel combination. Several PDX models from patients in clinical trials have been used to assess the efficacy of individual drugs or drug combinations in co-clinical trials.
Highlights
Cancer is the leading cause of death in economically developed countries, and many physicians and scientists are using their efforts to develop new treatment approaches
Articles were searched on 23 January, 2019 by PubMed online with the terms “Patient-derived xenograft (PDX) clinical trial” or “patient-derived xenograft clinical trial”, the articles of PDX models used for the research of tumor biology and/or drug development were not searched completely
A total of 106 articles and 253 articles were identified through PubMed search, using the terms “PDX clinical trial”
Summary
Cancer is the leading cause of death in economically developed countries, and many physicians and scientists are using their efforts to develop new treatment approaches. Surgery, radiation therapy, and chemotherapy are the three pillars for curing and prolonging survival of patients with cancer. Among these treatments, cancer chemotherapy plays a central role for patients with advanced or recurrent cancer. Conventional anti-cancer drugs can directly kill rapidly proliferating cells, while small molecule inhibitors and therapeutic antibodies can inhibit the intracellular growth signal cascade and lead to cancer cell-specific death [1,2]. For the development of anti-cancer drugs, in vitro cell killing assays using commercially available patient-derived cell lines or in vivo tumor growth inhibition assays using cell-line-derived xenograft (CDX) models are commonly employed to measure the efficacy of drugs and to make a “go or no-go” decision for further clinical study.
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