Prioritizing therapeutic targets using patient-derived xenograft models

K. A. Lodhia, A. M. Hadley, P. Haluska, C. L. Scott

Research output: Contribution to journalReview article

30 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)223-234
Number of pages12
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1855
Issue number2
DOIs
StatePublished - Apr 1 2015

Keywords

  • Genomics
  • Patient-derived xenografts
  • Personalized medicine
  • Targeted therapy
  • Therapeutic targets

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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