Prioritizing therapeutic targets using patient-derived xenograft models

Biochimica Et Biophysica Acta
K A LodhiaClare L Scott

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.

References

Apr 1, 1997·Laboratory Animals·S ShibataK Doi
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Apr 25, 2003·International Journal of Cancer. Journal International Du Cancer·Philipp BeckhoveVolker Schirrmacher
Jan 22, 2004·Archives of Medical Research·Albertus W WognumTerry E Thomas
Oct 21, 2005·The New England Journal of Medicine·Martine J Piccart-GebhartUNKNOWN Herceptin Adjuvant (HERA) Trial Study Team
Oct 21, 2005·The New England Journal of Medicine·Edward H RomondNorman Wolmark
May 25, 2006·Immunologic Research·Sebastian George Barton Furness, Kelly McNagny
Aug 11, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Belen Rubio-ViqueiraManuel Hidalgo
Jan 18, 2007·Journal of the National Cancer Institute·Ken Garber
Mar 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chie Kudo-SaitoJames W Hodge
Apr 5, 2007·Nature Protocols·Christopher L Morton, Peter J Houghton
Jul 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elisabetta MarangoniMarie-France Poupon
Jul 13, 2007·Nature Reviews. Cancer·Lloyd Kelland
Feb 1, 2008·Cell Cycle·Laurent Knoops, Daphne de Jong
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Iduna FichtnerJohannes Merk
Feb 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xin DongYuzhuo Wang
Mar 17, 2010·The Journal of Pathology·Ahmed Ashour AhmedJames D Brenton
May 13, 2010·Journal of Biomedical Science·Hsiang-Ling HuangHong-Lin Chan
Aug 4, 2010·Melanoma Research·Gabriela I RozenbergNorman E Sharpless
Oct 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Huiping LiuMichael F Clarke
Nov 26, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ursula KortmannC Blake Gilks
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Anand G PatelScott H Kaufmann
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jun 18, 2011·Cellular Oncology (Dordrecht)·Sandra Pérez-TorrasAdela Mazo
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Samantha R OakesGeoffrey J Lindeman
Jul 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Edith A PerezNorman Wolmark
Oct 29, 2011·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Gemma GattaUNKNOWN RARECARE working group
Mar 29, 2012·The New England Journal of Medicine·Jonathan LedermannUrsula Matulonis
Apr 18, 2012·Nature Reviews. Clinical Oncology·John J TentlerS Gail Eckhardt
May 24, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Thomas JohnMing-Sound Tsao
Jun 8, 2012·Science Translational Medicine·Sharanya SivanandJames Brugarolas
Jul 25, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sylvia JulienCyril Berthet
Aug 29, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·O J Finn
Oct 13, 2012·Journal of Hematology & Oncology·Shundong CangDelong Liu

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Citations

Dec 23, 2015·Trends in Genetics : TIG·Xueda Hu, Zemin Zhang
Aug 10, 2015·Biochimica Et Biophysica Acta·Emyr BakkerMarija Krstic-Demonacos
Jun 23, 2015·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Takahiro NakajimaKazuhiro Yasufuku
May 8, 2015·Nature Medicine·Stephen E GouldFrederic J de Sauvage
May 8, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Noriko KanayaShiuan Chen
Sep 18, 2016·Critical Reviews in Oncology/hematology·Marcello Maugeri-SaccàRuggero De Maria
Apr 27, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Delphine NicolleStefano Cairo
Jan 18, 2017·Biotechnology Journal·Kathrin Halfter, Barbara Mayer
Feb 9, 2017·Pharmacology & Therapeutics·Diana BehrensIduna Fichtner
Mar 3, 2018·Journal of Clinical Medicine·Juliet A Williams
Aug 22, 2018·International Journal of Molecular Sciences·Cristian P MoiolaEva Colas
Jan 18, 2017·Chemical Research in Toxicology·Karam El-BayoumyJoseph B Guttenplan

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