Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Abstract

Patient‐derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice, have emerged as a pivotal approach in translational research, particularly in advancing precision medicine. As the first stage of PDX development, the patient‐derived orthotopic xenograft (PDOX) models implant tumor tissue in mice in the corresponding anatomical locations of the patient. The PDOX models have several advantages, including high fidelity to the original tumor, heightened drug sensitivity, and an elevated rate of successful transplantation. However, the PDOX models present significant challenges, requiring advanced surgical techniques and resource‐intensive imaging technologies, which limit its application. And then, the humanized mouse models, as well as the zebrafish models, were developed. Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay. The humanized mouse models are a hot topic in PDX model research. Regarding zebrafish patient‐derived tumor xenografts (zPDX) and patient‐derived organoids (PDO) as promising models for studying cancer and drug discovery, zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time. PDO models provide a cost‐effective approach for drug testing that replicates the in vivo environment and preserves important tumor‐related information for patients. The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.

Navigating the Immune Maze: Pioneering Strategies for Unshackling Cancer Immunotherapy Resistance

“…Translational research tools like patient-derived organoids (PDOs) and xenograft models (PDX) are instrumental in applying preclinical findings to clinical treatment design. For instance, PDOs derived from colorectal cancer patients have been utilized to evaluate the efficacy of novel drugs, replicating the complex cellular environment of the originating tumor [153,154]. These studies have led directly to clinical trials and adjustments to treatment regimens, exemplifying how PDOs can significantly influence therapeutic planning and patient management.…”

“…PDX models, together with PDOs, enhance therapeutic planning by replicating the complex tumor environment, thereby offering a dynamic platform for drug evaluation and the development of personalized treatment regimens [153,154].…”

Translation of Data from Animal Models of Cancer to Immunotherapy of Breast Cancer and Chronic Lymphocytic Leukemia

“…Patient-derived tumor xenograft (PDX) models [ 21 ], which involve the transplantation of tumor tissues derived from cancer patients into immunodeficient mice, have also become a prominent weapon in the armamentarium fostering translational research, particularly for solid tumors. Initially, orthotopic xenograft (PDOX) models were used, where tumor tissue was implanted in mice in anatomical locations that corresponded to that in the patient.…”

Dclre1c-Mutation-Induced Immunocompromised Mice Are a Novel Model for Human Xenograft Research

“…Xenograft models, wherein human tissues or cells are grafted into animal hosts, are pivotal for oncological and immunological research. The choice of laboratory animal is critical to the success of xenografts, with immunodeficient strains being preferred due to their diminished immune cell function and consequent lower rejection rates of foreign tissues than immunocompetent mice [6][7][8]. Commonly utilized strains, such as nude mice, NOD-SCID and NSG mice, offer utility in xenograft applications, but are hampered by poor maternal behaviors and stringent environmental requirements for their upkeep.…”