Related Experiment Video
Updated: Apr 16, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Prioritizing therapeutic targets using patient-derived xenograft models
K A Lodhia1, A M Hadley2, P Haluska1
1Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Abstract:
Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDXs) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximize insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design.
Insights
Patient-derived xenografts (PDXs) help personalize cancer therapy by modeling individual tumors. These models aid in identifying effective treatments and predicting drug resistance, advancing precision oncology.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Personalized cancer therapy requires identifying and targeting key tumor-driving molecular targets.
- Validated molecular targets for cancer treatment remain limited despite advances in genomic medicine.
Purpose of the Study:
- To highlight the utility of patient-derived xenografts (PDXs) in advancing personalized cancer treatment.
- To address challenges and maximize the clinical insights gained from PDX models.
Main Methods:
- Development of PDX models using direct patient tumor implantation in immunocompromised mice.
- Focus on immune system humanization within PDX models.
- Emphasis on high-quality molecular annotation of PDX models.
Main Results:
- PDX models serve as powerful patient surrogates for evaluating individualized cancer therapies.
- Repeated and parallel sampling of PDX models reveals tumor clonal evolution.
- Clonal evolution insights can predict drug resistance mechanisms and inform therapeutic strategies.
Conclusions:
- PDX models are crucial for optimizing systemic cancer treatment delivery and therapeutic potential.
- Addressing PDX model challenges is key to maximizing their clinical applicability in precision oncology.
- PDX models facilitate the design of effective therapeutic strategies by predicting resistance and guiding treatment selection.
