Patient-derived tumour xenografts as models for oncology drug development

By J. Tentler, A. Tan, C. Weekes, A. Jimeno, S. Leong, T. Pitts, J. Arcaroli, W. Messersmith, S. Eckhardt. Nature Reviews Clinical Oncology, 2012

1,207 citations recorded by the source corpus.

Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.

Subfields: Biomedical Engineering, Biotechnology, Oncology

View Paper: https://www.semanticscholar.org/paper/7f3d131f092a3d02c965b0c2bc08a5fbfeed75db

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. C. Szabó
2. J. Seoane
3. R. DePinho

Citations in the corpus

• Systems biology approaches for advancing the discovery of effective drug combinations (2015, background): “Predicted drug combinations should be validated in cancer cell lines and in relevant in vivo human disease models such as patient-derived tumor xenografts [81].”
• Genetics and biology of prostate cancer (2018, background): “Patient-derived xenograft (PDX) models also provide a complementary system for investigating the molecular mechanisms underlying tumor progression and therapeutic resistance, predicting clinical outcomes and informing treatment plans, and guiding drug development across many cancer types (Tentler et”
• Prospective derivation of a Living Organoid Biobank of colorectal cancer patients (2015, neutral): “, 2013), and xeno-transplantation of the tumor into immunodeficient mice (Jin et al., 2010; Tentler et al., 2012).”
• Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research (2014, background): “Over the last few years, there has been a growing interest in developing PDX collections and using them for different cancer research applications (11, 12).”
• Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer (2013, background): “The patient-derived tumor xenograft (PDTX) is an emerging preclinical model for anticancer drug development, because it more closely recapitulates both the genetic and cellular heterogeneity of the patient’s original tumor tissue (22) (Fig.”