Challenges and Prospects of Patient-Derived Xenografts for Cancer Research

Abstract

We discuss the importance of the in vivo models in elucidating cancer biology, focusing on the patient-derived xenograft (PDX) models, which are classic and standard functional in vivo platforms for preclinical evaluation. We provide an overview of the most representative models, including cell-derived xenografts (CDX), tumor and metastatic cell-derived xenografts, and PDX models utilizing humanized mice (HM). The orthotopic models, which could reproduce the cancer environment and its progression, similar to human tumors, are particularly common. The standard procedures and rationales of gastric adenocarcinoma (GAC) orthotopic models are addressed. Despite the significant advantages of the PDX models, such as recapitulating key features of human tumors and enabling drug testing in the in vivo context, some challenges must be acknowledged, including loss of heterogeneity, selection bias, clonal evolution, stroma replacement, tumor micro-environment (TME) changes, host cell carryover and contaminations, human-to-host cell oncogenic transformation, human and host viral infections, as well as limitations for immunologic research. To compensate for these limitations, other mouse models, such as syngeneic and humanized mouse models, are currently utilized. Overall, the PDX models represent a powerful tool in cancer research, providing critical insights into tumor biology and potential therapeutic targets, but their limitations and challenges must be carefully considered for their effective use. Lastly, we present an intronic quantitative PCR (qPCR) method to authenticate, detect, and quantify human/murine cells in cell lines and PDX samples.

Application of Epithelial Growth Factor Receptor-Targeted Magnetic Resonance Imaging and Near-Infrared II Dual-Modal Probe in Lung Cancer Diagnosis and Surgical Resection

“…NIR-II optical imaging was conducted in a PDX mouse model. The PDX model had the advantage of retaining tumor heterogeneity, mutations, and tumor microenvironment . The PDX mice were categorized into experimental, isotype, and block groups.…”

LncRNA GAS6-AS1 contributes to 5-fluorouracil resistance in colorectal cancer

“…Considering the significant regulation of GAS6-AS1 on 5-FU resistance in CRC, we next explore the possibility of combination therapy targeted on GAS6-AS1 and 5-FU in vivo. PDX model doesn’t undergo the screening process of in vitro culture, could maintain the original characteristics and heterogeneity of tumors, sustain molecular biology stability and preserve the original non tumor matrix and microenvironment of tumor tissue(Heinrich, Mostafa et al, 2021, Jin, Yoshimura et al, 2023, Zanella, Grassi et al, 2022). Thereby, PDX model was suitable for evaluating drug efficacy.…”

SERS in 3D cell models: a powerful tool in cancer research

“…5,80,81 With PDX models, one also faces the challenge that engraftment success rate can vary wildly, often leading to the loss of difficult-to-obtain patient-derived samples. 82 Ultimately, these drawbacks have promoted research interest in human tissue engineering. 83 However, until now, owing to their high engraftment success rates with commercial cell lines and their ability to replicate tumor microenvironments with good fidelity, xenograft models have enabled significant developments in the design and implementation of SERS probes in 3D, which will be discussed further in Sections 3 and 4.…”