Patient-derived xenograft (PDX) models, in which tumor tissues from patients are implanted into immunocompromised or humanized mice, have shown superiority in recapitulating the characteristics of cancer, such as the spatial structure of cancer and the intratumor heterogeneity of cancer. Moreover, PDX models retain the genomic features of patients across different stages, subtypes, and diversified treatment backgrounds. Optimized PDX engraftment procedures and modern technologies such as multi-omics and deep learning have enabled a more comprehensive depiction of the PDX molecular landscape and boosted the utilization of PDX models. These irreplaceable advantages make PDX models an ideal choice in cancer treatment studies, such as preclinical trials of novel drugs, validating novel drug combinations, screening drug-sensitive patients, and exploring drug resistance mechanisms. In this review, we gave an overview of the history of PDX models and the process of PDX model establishment. Subsequently, the review presents the strengths and weaknesses of PDX models and highlights the integration of novel technologies in PDX model research. Finally, we delineated the broad application of PDX models in chemotherapy, targeted therapy, immunotherapy, and other novel therapies. 

/pdf/patient-derived-xenograft-models-in-cancer-therapy-2fyw6tfm.pdf

Patient-derived xenograft models in cancer therapy: technologies and applications

Towards precision oncology with patient-derived xenografts

Molecularly targeted treatments and immunotherapy are cornerstones in oncology, with demonstrated efficacy across different tumor types. Nevertheless, the overwhelming majority metastatic disease is incurable due to the onset of drug resistance. Preclinical models including genetically engineered mouse models, patient-derived xenografts and two- and three-dimensional cell cultures have emerged as a useful resource to study mechanisms of cancer progression and predict efficacy of anticancer drugs. However, variables including tumor heterogeneity and the complexities of the microenvironment can impair the faithfulness of these platforms. Here, we will discuss advantages and limitations of these preclinical models, their applicability for drug testing and in co-clinical trials and potential strategies to increase their reliability in predicting responsiveness to anticancer medications.

/pdf/patient-derived-cancer-models-valuable-platforms-for-300jrrz4.pdf

Patient-derived cancer models: Valuable platforms for anticancer drug testing

Abstract PDCM Finder (www.cancermodels.org) is a cancer research platform that aggregates clinical, genomic and functional data from patient-derived xenografts, organoids and cell lines. It was launched in April 2022 as a successor of the PDX Finder portal, which focused solely on patient-derived xenograft models. Currently the portal has over 6200 models across 13 cancer types, including rare paediatric models (17%) and models from minority ethnic backgrounds (33%), making it the largest free to consumer and open access resource of this kind. The PDCM Finder standardises, harmonises and integrates the complex and diverse data associated with PDCMs for the cancer community and displays over 90 million data points across a variety of data types (clinical metadata, molecular and treatment-based). PDCM data is FAIR and underpins the generation and testing of new hypotheses in cancer mechanisms and personalised medicine development.

PDCM Finder: an open global research platform for patient-derived cancer models

Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive tumor behavior and poor prognosis. Recent next-generation sequencing (NGS)-based genomic studies have provided novel treatment modes for pancreatic cancer via the identification of cancer driver variants and molecular subtypes in PDAC. Genome-wide approaches have been extended to model systems such as patient-derived xenografts (PDXs), organoids, and cell lines for pre-clinical purposes. However, the genomic characteristics vary in the model systems, which is mainly attributed to the clonal evolution of cancer cells during their construction and culture. Moreover, fundamental limitations such as low tumor cellularity and the complex tumor microenvironment of PDAC hinder the confirmation of genomic features in the primary tumor and model systems. The occurrence of these phenomena and their associated complexities may lead to false insights into the understanding of mechanisms and dynamics in tumor tissues of patients. In this review, we describe various model systems and discuss differences in the results based on genomics and transcriptomics between primary tumors and model systems. Finally, we introduce practical strategies to improve the accuracy of genomic analysis of primary tissues and model systems. 

https://doi.org/10.1016/j.csbj.2022.08.064

Challenges in genomic analysis of model systems and primary tumors of pancreatic ductal adenocarcinoma

Patient-derived xenografts (PDX) mice models play an important role in preclinical trials and personalized medicine. Sharing data on the models is highly valuable for numerous reasons - ethical, economical, research cross validation etc. The EurOPDX Consortium was established 8 years ago to share such information and avoid duplicating efforts in developing new PDX mice models and unify approaches to support preclinical research. EurOPDX Data Portal is the unified data sharing platform adopted by the Consortium.In this paper we describe the main features of the EurOPDX Data Portal ( https://dataportal.europdx.eu/ ), its architecture and possible utilization by researchers who look for PDX mice models for their research. The Portal offers a catalogue of European models accessible on a cooperative basis. The models are searchable by metadata, and a detailed view provides molecular profiles (gene expression, mutation, copy number alteration) and treatment studies. The Portal displays the data in multiple tools (PDX Finder, cBioPortal, and GenomeCruzer in future), which are populated from a common database displaying strictly mutually consistent views.EurOPDX Data Portal is an entry point to the EurOPDX Research Infrastructure offering PDX mice models for collaborative research, (meta)data describing their features and deep molecular data analysis according to users' interests. 

/pdf/the-europdx-data-portal-an-open-platform-for-patient-derived-8rt5gep4.pdf

The EurOPDX Data Portal: an open platform for patient-derived cancer xenograft data sharing and visualization

/pdf/the-europdx-data-portal-an-open-platform-for-patient-derived-1m0rgsos.pdf

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The EurOPDX Data Portal: an open platform for patient-derived cancer xenograft data sharing and visualization

The EurOPDX Data Portal: an open platform for patient-derived cancer xenograft data sharing and visualization