REFLECT - PRospective Evaluation of Freshly ImpLantEd Cancers in Mice to Test Drug Response in Matching Host

Aims/Goals:

  1. To evaluate feasibility of prospective pPDX generation, drug sensitivity testing and data integration from (i) surgical samples following neoadjuvant chemotherapy; (ii) biopsies or surgical resection of metastatic lesions  

  1. To provide information about the drug sensitivity of patients’ tumours when grown as personalized patient derived xenografts that could complement tumour molecular profiling information to guide treatment selection. 

  1. To compare genomic alterations in clinical and pPDX samples 

  1. To identify mechanisms of acquired drug resistance in pPDX and determine if these reflect clinical findings

 

Summary

Rapid advances in genomic characterization technologies have made clinical sequencing feasible, such that profiling of patient tumour samples to identify “actionable mutations” (defined here as alterations that predict or confer sensitivity or resistance to a drug) is being rapidly adopted, with the goal of identifying potential treatment strategies based on individual tumour characteristics. It is possible, however, that the success of genomic-based predictive biomarkers may be limited by several factors, including intra-tumoural heterogeneity, the multiplicity of genetic aberrations that occur in human cancers, the presence of epigenetic alterations and other potential modifiers of tumour response. In many cases, the predictive value of mutations for drug response are unknown. One alternate approach that has been proposed to help guide the selection of therapy for individual patients is the application of in vivo drug testing in personalized patient-derived xenografts (pPDX) – which are laboratory models of an individual’s cancer grown and expanded in cohorts of immunocompromised mice.  This provides an opportunity to assess impact of a variety of drugs on in vivo tumour growth.

Key Researchers