title: Prioritizing therapeutic targets using patient-derived xenograft models.
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.
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Lodhia
authors.affiliation: Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Hadley
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, MN, USA.
authors.forename: P
authors.initials: P
authors.lastname: Haluska
authors.affiliation: Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. Electronic address: scottc@wehi.edu.au.
authors.forename: C L
authors.initials: CL
authors.lastname: Scott
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000276:immunology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D057285:Precision Medicine; D023041:Xenograft Model Antitumor Assays
keywords: Genomics; Patient-derived xenografts; Personalized medicine; Targeted therapy; Therapeutic targets