The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

Elizabeth C. Townsend; Mark A. Murakami; Alexandra Christodoulou; Amanda L. Christie; Johannes Köster; Tiffany A. DeSouza; Elizabeth A. Morgan; Scott P. Kallgren; Huiyun Liu; Shuo Chieh Wu; Olivia Plana; Joan Montero; Kristen E. Stevenson; Prakash Rao; Raga Vadhi; Michael Andreeff; Philippe Armand; Karen K. Ballen; Patrizia Barzaghi-Rinaudo; Sarah Cahill; Rachael A. Clark; Vesselina G. Cooke; Matthew S. Davids; Daniel J. DeAngelo; David M. Dorfman; Hilary Eaton; Benjamin L. Ebert; Julia Etchin; Brant Firestone; David C. Fisher; Arnold S. Freedman; Ilene A. Galinsky; Hui Gao; Jacqueline S. Garcia; Francine Garnache-Ottou; Timothy A. Graubert; Alejandro Gutierrez; Ensar Halilovic; Marian H. Harris; Zachary T. Herbert; Steven M. Horwitz; Giorgio Inghirami; Andrew M. Intlekoffer; Moriko Ito; Shai Izraeli; Eric D. Jacobsen; Caron A. Jacobson; Sébastien Jeay; Irmela Jeremias; Michelle A. Kelliher; Raphael Koch; Marina Konopleva; Nadja Kopp; Steven M. Kornblau; Andrew L. Kung; Thomas S. Kupper; Nicole LaBoeuf; Ann S. LaCasce; Emma Lees; Loretta S. Li; A. Thomas Look; Masato Murakami; Markus Muschen; Donna Neuberg; Samuel Y. Ng; Oreofe O. Odejide; Stuart H. Orkin; Rachel R. Paquette; Andrew E. Place; Justine E. Roderick; Jeremy A. Ryan; Stephen E. Sallan; Brent Shoji; Lewis B. Silverman; Robert J. Soiffer; David P. Steensma; Kimberly Stegmaier; Richard M. Stone; Jerome Tamburini; Aaron R. Thorner; Paul van Hummelen; Martha Wadleigh; Marion Wiesmann; Andrew P. Weng; Jens U. Wuerthner; David A. Williams; Bruce M. Wollison; Andrew A. Lane; Anthony Letai; Monica M. Bertagnolli; Jerome Ritz; Myles Brown; Henry Long; Jon C. Aster; Margaret A. Shipp; James D. Griffin; David M. Weinstock

doi:10.1016/j.ccell.2016.03.008

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

Elizabeth C. Townsend, Mark A. Murakami, Alexandra Christodoulou, Amanda L. Christie, Johannes Köster, Tiffany A. DeSouza, Elizabeth A. Morgan, Scott P. Kallgren, Huiyun Liu, Shuo Chieh Wu, Olivia Plana, Joan Montero, Kristen E. Stevenson, Prakash Rao, Raga Vadhi, Michael Andreeff, Philippe Armand, Karen K. Ballen, Patrizia Barzaghi-Rinaudo, Sarah CahillRachael A. Clark, Vesselina G. Cooke, Matthew S. Davids, Daniel J. DeAngelo, David M. Dorfman, Hilary Eaton, Benjamin L. Ebert, Julia Etchin, Brant Firestone, David C. Fisher, Arnold S. Freedman, Ilene A. Galinsky, Hui Gao, Jacqueline S. Garcia, Francine Garnache-Ottou, Timothy A. Graubert, Alejandro Gutierrez, Ensar Halilovic, Marian H. Harris, Zachary T. Herbert, Steven M. Horwitz, Giorgio Inghirami, Andrew M. Intlekoffer, Moriko Ito, Shai Izraeli, Eric D. Jacobsen, Caron A. Jacobson, Sébastien Jeay, Irmela Jeremias, Michelle A. Kelliher, Raphael Koch, Marina Konopleva, Nadja Kopp, Steven M. Kornblau, Andrew L. Kung, Thomas S. Kupper, Nicole LaBoeuf, Ann S. LaCasce, Emma Lees, Loretta S. Li, A. Thomas Look, Masato Murakami, Markus Muschen, Donna Neuberg, Samuel Y. Ng, Oreofe O. Odejide, Stuart H. Orkin, Rachel R. Paquette, Andrew E. Place, Justine E. Roderick, Jeremy A. Ryan, Stephen E. Sallan, Brent Shoji, Lewis B. Silverman, Robert J. Soiffer, David P. Steensma, Kimberly Stegmaier, Richard M. Stone, Jerome Tamburini, Aaron R. Thorner, Paul van Hummelen, Martha Wadleigh, Marion Wiesmann, Andrew P. Weng, Jens U. Wuerthner, David A. Williams, Bruce M. Wollison, Andrew A. Lane, Anthony Letai, Monica M. Bertagnolli, Jerome Ritz, Myles Brown, Henry Long, Jon C. Aster, Margaret A. Shipp, James D. Griffin, David M. Weinstock^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

202 Scopus citations

Abstract

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

Original language	English
Pages (from-to)	574-586
Number of pages	13
Journal	Cancer Cell
Volume	29
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2016.03.008
State	Published - 11 Apr 2016

Funding

Funders	Funder number
National Institute of Arthritis and Musculoskeletal and Skin Diseases	P30AR069625
Damon Runyon Cancer Research Foundation
Novartis
Gabrielle’s Angel Foundation for Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2016.03.008

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Townsend, E. C., Murakami, M. A., Christodoulou, A., Christie, A. L., Köster, J., DeSouza, T. A., Morgan, E. A., Kallgren, S. P., Liu, H., Wu, S. C., Plana, O., Montero, J., Stevenson, K. E., Rao, P., Vadhi, R., Andreeff, M., Armand, P., Ballen, K. K., Barzaghi-Rinaudo, P., ... Weinstock, D. M. (2016). The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell, 29(4), 574-586. https://doi.org/10.1016/j.ccell.2016.03.008

@article{da289d91ba4f45399cdf7b80586d663f,

title = "The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice",

abstract = "More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.",

author = "Townsend, {Elizabeth C.} and Murakami, {Mark A.} and Alexandra Christodoulou and Christie, {Amanda L.} and Johannes K{\"o}ster and DeSouza, {Tiffany A.} and Morgan, {Elizabeth A.} and Kallgren, {Scott P.} and Huiyun Liu and Wu, {Shuo Chieh} and Olivia Plana and Joan Montero and Stevenson, {Kristen E.} and Prakash Rao and Raga Vadhi and Michael Andreeff and Philippe Armand and Ballen, {Karen K.} and Patrizia Barzaghi-Rinaudo and Sarah Cahill and Clark, {Rachael A.} and Cooke, {Vesselina G.} and Davids, {Matthew S.} and DeAngelo, {Daniel J.} and Dorfman, {David M.} and Hilary Eaton and Ebert, {Benjamin L.} and Julia Etchin and Brant Firestone and Fisher, {David C.} and Freedman, {Arnold S.} and Galinsky, {Ilene A.} and Hui Gao and Garcia, {Jacqueline S.} and Francine Garnache-Ottou and Graubert, {Timothy A.} and Alejandro Gutierrez and Ensar Halilovic and Harris, {Marian H.} and Herbert, {Zachary T.} and Horwitz, {Steven M.} and Giorgio Inghirami and Intlekoffer, {Andrew M.} and Moriko Ito and Shai Izraeli and Jacobsen, {Eric D.} and Jacobson, {Caron A.} and S{\'e}bastien Jeay and Irmela Jeremias and Kelliher, {Michelle A.} and Raphael Koch and Marina Konopleva and Nadja Kopp and Kornblau, {Steven M.} and Kung, {Andrew L.} and Kupper, {Thomas S.} and Nicole LaBoeuf and LaCasce, {Ann S.} and Emma Lees and Li, {Loretta S.} and Look, {A. Thomas} and Masato Murakami and Markus Muschen and Donna Neuberg and Ng, {Samuel Y.} and Odejide, {Oreofe O.} and Orkin, {Stuart H.} and Paquette, {Rachel R.} and Place, {Andrew E.} and Roderick, {Justine E.} and Ryan, {Jeremy A.} and Sallan, {Stephen E.} and Brent Shoji and Silverman, {Lewis B.} and Soiffer, {Robert J.} and Steensma, {David P.} and Kimberly Stegmaier and Stone, {Richard M.} and Jerome Tamburini and Thorner, {Aaron R.} and {van Hummelen}, Paul and Martha Wadleigh and Marion Wiesmann and Weng, {Andrew P.} and Wuerthner, {Jens U.} and Williams, {David A.} and Wollison, {Bruce M.} and Lane, {Andrew A.} and Anthony Letai and Bertagnolli, {Monica M.} and Jerome Ritz and Myles Brown and Henry Long and Aster, {Jon C.} and Shipp, {Margaret A.} and Griffin, {James D.} and Weinstock, {David M.}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = apr,

day = "11",

doi = "10.1016/j.ccell.2016.03.008",

language = "אנגלית",

volume = "29",

pages = "574--586",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

}

Townsend, EC, Murakami, MA, Christodoulou, A, Christie, AL, Köster, J, DeSouza, TA, Morgan, EA, Kallgren, SP, Liu, H, Wu, SC, Plana, O, Montero, J, Stevenson, KE, Rao, P, Vadhi, R, Andreeff, M, Armand, P, Ballen, KK, Barzaghi-Rinaudo, P, Cahill, S, Clark, RA, Cooke, VG, Davids, MS, DeAngelo, DJ, Dorfman, DM, Eaton, H, Ebert, BL, Etchin, J, Firestone, B, Fisher, DC, Freedman, AS, Galinsky, IA, Gao, H, Garcia, JS, Garnache-Ottou, F, Graubert, TA, Gutierrez, A, Halilovic, E, Harris, MH, Herbert, ZT, Horwitz, SM, Inghirami, G, Intlekoffer, AM, Ito, M, Izraeli, S, Jacobsen, ED, Jacobson, CA, Jeay, S, Jeremias, I, Kelliher, MA, Koch, R, Konopleva, M, Kopp, N, Kornblau, SM, Kung, AL, Kupper, TS, LaBoeuf, N, LaCasce, AS, Lees, E, Li, LS, Look, AT, Murakami, M, Muschen, M, Neuberg, D, Ng, SY, Odejide, OO, Orkin, SH, Paquette, RR, Place, AE, Roderick, JE, Ryan, JA, Sallan, SE, Shoji, B, Silverman, LB, Soiffer, RJ, Steensma, DP, Stegmaier, K, Stone, RM, Tamburini, J, Thorner, AR, van Hummelen, P, Wadleigh, M, Wiesmann, M, Weng, AP, Wuerthner, JU, Williams, DA, Wollison, BM, Lane, AA, Letai, A, Bertagnolli, MM, Ritz, J, Brown, M, Long, H, Aster, JC, Shipp, MA, Griffin, JD & Weinstock, DM 2016, 'The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice', Cancer Cell, vol. 29, no. 4, pp. 574-586. https://doi.org/10.1016/j.ccell.2016.03.008

TY - JOUR

T1 - The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

AU - Townsend, Elizabeth C.

AU - Murakami, Mark A.

AU - Christodoulou, Alexandra

AU - Christie, Amanda L.

AU - Köster, Johannes

AU - DeSouza, Tiffany A.

AU - Morgan, Elizabeth A.

AU - Kallgren, Scott P.

AU - Liu, Huiyun

AU - Wu, Shuo Chieh

AU - Plana, Olivia

AU - Montero, Joan

AU - Stevenson, Kristen E.

AU - Rao, Prakash

AU - Vadhi, Raga

AU - Andreeff, Michael

AU - Armand, Philippe

AU - Ballen, Karen K.

AU - Barzaghi-Rinaudo, Patrizia

AU - Cahill, Sarah

AU - Clark, Rachael A.

AU - Cooke, Vesselina G.

AU - Davids, Matthew S.

AU - DeAngelo, Daniel J.

AU - Dorfman, David M.

AU - Eaton, Hilary

AU - Ebert, Benjamin L.

AU - Etchin, Julia

AU - Firestone, Brant

AU - Fisher, David C.

AU - Freedman, Arnold S.

AU - Galinsky, Ilene A.

AU - Gao, Hui

AU - Garcia, Jacqueline S.

AU - Garnache-Ottou, Francine

AU - Graubert, Timothy A.

AU - Gutierrez, Alejandro

AU - Halilovic, Ensar

AU - Harris, Marian H.

AU - Herbert, Zachary T.

AU - Horwitz, Steven M.

AU - Inghirami, Giorgio

AU - Intlekoffer, Andrew M.

AU - Ito, Moriko

AU - Izraeli, Shai

AU - Jacobsen, Eric D.

AU - Jacobson, Caron A.

AU - Jeay, Sébastien

AU - Jeremias, Irmela

AU - Kelliher, Michelle A.

AU - Koch, Raphael

AU - Konopleva, Marina

AU - Kopp, Nadja

AU - Kornblau, Steven M.

AU - Kung, Andrew L.

AU - Kupper, Thomas S.

AU - LaBoeuf, Nicole

AU - LaCasce, Ann S.

AU - Lees, Emma

AU - Li, Loretta S.

AU - Look, A. Thomas

AU - Murakami, Masato

AU - Muschen, Markus

AU - Neuberg, Donna

AU - Ng, Samuel Y.

AU - Odejide, Oreofe O.

AU - Orkin, Stuart H.

AU - Paquette, Rachel R.

AU - Place, Andrew E.

AU - Roderick, Justine E.

AU - Ryan, Jeremy A.

AU - Sallan, Stephen E.

AU - Shoji, Brent

AU - Silverman, Lewis B.

AU - Soiffer, Robert J.

AU - Steensma, David P.

AU - Stegmaier, Kimberly

AU - Stone, Richard M.

AU - Tamburini, Jerome

AU - Thorner, Aaron R.

AU - van Hummelen, Paul

AU - Wadleigh, Martha

AU - Wiesmann, Marion

AU - Weng, Andrew P.

AU - Wuerthner, Jens U.

AU - Williams, David A.

AU - Wollison, Bruce M.

AU - Lane, Andrew A.

AU - Letai, Anthony

AU - Bertagnolli, Monica M.

AU - Ritz, Jerome

AU - Brown, Myles

AU - Long, Henry

AU - Aster, Jon C.

AU - Shipp, Margaret A.

AU - Griffin, James D.

AU - Weinstock, David M.

PY - 2016/4/11

Y1 - 2016/4/11

N2 - More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

AB - More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

UR - http://www.scopus.com/inward/record.url?scp=84962740421&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2016.03.008

DO - 10.1016/j.ccell.2016.03.008

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 27070704

AN - SCOPUS:84962740421

SN - 1535-6108

VL - 29

SP - 574

EP - 586

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

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