Patient-Derived Xenograft models undergo mouse-specific tumour evolution

PDX models are in vivo systems to study human cancers and tumour therapies. Identifying the correct PDX models for developing drug targets is not an easy task for oncologists.
A recent scientific publication in Nature Genetics has highlighted the importance of cataloguing the molecular characterisation of PDX models.

Uri Ben-Davis and colleagues, from the Broad Institute (Massachusetts, USA), gathered 1,110 PDX samples from 24 cancer types to analyse the landscape of Copy Number Alterations (CNAs) in PDX models across multiple human cancers. They used these data to characterise CNA dynamics during PDX derivation and propagation.

The authors found that the unstable genome in many tumours continues to change after implantation into the mouse, and can accumulate mutations that differ in behaviour and response to chemotherapeutics from the original patient tumour. These findings have important implications when using PDXs as avatar models for personalised medicine.

Ben-Davis and colleagues suggest that it is necessary to ensure that the PDX model retains the relevant genomic features of the primary tumour before drug testing. The authors also highlight the following advice: i) avoid PDX prolonged propagation in order to prevent under-representation of some hallmark cancer events, ii) document and catalogue the molecular properties of the tumour in order to capture genomic landscape changes, and iii) include large cohorts of PDX models, similar to the large cell line collections, in order to average out random effects when performing drug screens and biomarker studies.

Repositive offers an online Global PDX Directory for oncology researchers to discover and compare PDX models. Working together with the Consortium members, we are creating a global catalogue of genomic and molecular characteristics of PDX models to help researchers compare and select the most suitable models for their research and speed up the translation from scientific advances to benefit cancer patients.

I am grateful to Repositive employee Anaid Diaz for her valuable input and edits to this entry.

Read more posts by Manuel Corpas