Systematic Review of Patient-Derived Xenograft Models for Preclinical Studies of Anti-Cancer Drugs in Solid Tumors

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.

Keywords: PDX clinical trial; co-clinical trial; drug development; drug sensitivity; patient-derived cancer model; solid tumor.

Figure 1

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow diagram of the article selection process.

Figure 2

Number of articles published in each year.

Figure 3

Cancer types used for patient-derived xenograft (PDX) models. The number of PDX models for each organ is shown for all periods (a), the first period from 2010 to 2016 (b), and the second period from 2017 onwards (c).

Figure 4

Mouse strains used for PDX models. The number of PDX models for each mouse strain is shown for all periods (a), the first period from 2010 to 2016 (b), and the second period from 2017 onwards (c).

Figure 5

Implantation sites of cancer tissues for PDX models. The number of PDX models for each implantation site is shown for all periods (a), the first period from 2010 to 2016 (b), and the second period from 2017 onwards (c).

Figure 6

Application of PDX models in cancer research. The number of PDX models for each application is shown during all periods (a), the first period from 2010 to 2016 (b), and the second period from 2017 onwards (c).