Table 4 Limitations and future perspectives of PDX models

Experiment design

No uniform standards in different research groups regarding patient information collection, required mouse strains and model numbers, endpoint selection, positive results definition, and data interpretation

Construct multicenter collaborative network; explore and establish a proper standard

Technical issues

1. Low success rate and high cost of engraftment

2. Long time frame: from engraftment to preclinical test and clinical application

3. Limited assessment tools for monitoring PDX tumor growth and response to therapies

1. Expand tumor sampling method (CTCs); define the best engraftment site (subcutaneous, orthotopic, renal cell capsule) or develop new approach; use PDOs to generate PDXs

2. Explore proper intra- and post- engraftment manipulations

3. Develop noninvasive and cost-effective tools for assessing tumor status

Intrinsic defects

1. Severe immunocompromised host: unsuitable for testing immunotherapy

2. Rapidly stroma substitution: change in the tumor microenvironment; unsuitable for screening agents against stroma elements

3. Dissimilar pharmacokinetics: over- or underestimation of antitumor drug efficacy

4. Tumor selection and evolution: genotype and phenotype alteration across passages

1. Develop immunocompetent models for establishing PDXs: reconstruct human immune system in immunocompromised models; induce immune tolerance to individual tumors in immunocompetent models; use knock-in or novel gene editing technologies generate genetically humanized mice

2. Mimic human tumor environment: inject immortalized human stromal cells

3. Identify the differences between PDX models and humans regrading drug pharmacology

4. Multiple-spot sampling and sample cryopreservation