Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment
Authors: Sun Hua , Cao Song , Mashl R. Jay , Mo Chia-Kuei , Zaccaria Simone , Wendl Michael C. , Davies Sherri R. , Bailey Matthew H. , Primeau Tina M. , Hoog Jeremy , Mudd Jacqueline L. , Dean Dennis A. , Patidar Rajesh , Chen Li , Wyczalkowski Matthew A. , Jayasinghe Reyka G. , Rodrigues Fernanda Martins , Terekhanova Nadezhda V. , Li Yize , Lim Kian-Huat , Wang-Gillam Andrea , Van Tine Brian A. , Ma Cynthia X. , Aft Rebecca , Fuh Katherine C. , Schwarz Julie K. , Zevallos Jose P. , Puram Sidharth V. , Dipersio John F. ,   The NCI PDXNet Consortium, Belmar Julie , Held Jason , Luo Jingqin , Van Tine Brian A. , Tipton Rose , Wu Yige , Yao Lijun , Zhou Daniel Cui , Butterfield Andrew , Chu Zhengtao , Fujita Maihi , Yang Chieh-Hsiang , Cortes-Sanchez Emilio , Scherer Sandra , Zhao Ling , Borovski Tijana , Chin Vicki , DiGiovanna John , Frech Christian , Grover Jeffrey , Jeon Ryan , Koc Soner , Randjelovic Jelena , Seepo Sara , Stankovic Tamara , Dobrolecki Lacey E. , Ittmann Michael , Hilsenbeck Susan G. , O’Malley Bert W. , Mitsiades Nicholas , Kaochar Salma , Akcakanat Argun , Augustine Jithesh , Chen Huiqin , Dai Bingbing , Evans Kurt W. , Gale Kelly , Gibbons Don , Ha Min Jin , Jensen Vanessa , Kim Michael , Kirby Bryce P. , Kopetz Scott , Lanier Christopher D. , Li Dali , Majidi Mourad , Menter David , Meraz Ismail , Saridogan Turcin , Scott Stephen , Sorokin Alexey , Tapia Coya , Wang Jing , Westin Shannon , Xi Yuanxin , Xu Yi , Yang Fei , Yap Timothy A. , Yennu-Nanda Vashisht G. , Yuca Erkan , Zhang Jianhua , Zhang Ran , Zhang Xiaoshan , Zheng Xiaofeng , Fingerman Dylan , Lin Haiyin , Liu Qin , Kossenkov Andrew V. , Rebecca Vito W. , Somasundaram Rajasekharan , Tetzlaff Michae T. , Wickramasinghe Jayamanna , Xiao Min , Xu Xiaowei , Bult Carol J. , Robinson Peter N. , Srivastava Anuj , Lloyd Michael W. , Neuhauser Steven B. , Rubinstein Jill , Sanderson Brian J. , White Brian , Woo Xing Yi , Wallace Tiffany , Minna John D. , Boning Gao , Girard Luc , Park Hyunsil , Timmons Brenda C. , Nathanson Katherine L. , Xu George , Pan Chong-xian , Chen Jr Moon S. , Carvajal-Carmona Luis G. , Cho May , Coggins Nicole B. , White Ralph W. deVere , Polanco-Echeverry Guadalupe , Estrada Ana , Gandara David R. , Kirane Amanda R. , Le Tiffany , Lott Paul , Arana Alexa Morales , Reiss Jonathan W. , Rocha Sienna , Tepper Clifford G. , Toal Ted , Zhang Hongyong , Ma Ai-Hong , Davis-Dusenbery Brandi , Ellis Matthew J. , Lewis Michael T. , Davies Michael A. , Herlyn Meenhard , Fang Bingliang , Roth Jack A. , Welm Alana L. , Welm Bryan E. , Meric-Bernstam Funda , Chen Feng , Fields Ryan C. , Li Shunqiang , Govindan Ramaswamy , Doroshow James H. , Moscow Jeffrey A. , Evrard Yvonne A. , Chuang Jeffrey H. , Raphael Benjamin J. , Ding Li 
Published: August 2021

AbstractDevelopment of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors.