Journal ArticleDOI
Spectrum of genomic alterations in FGFR3: current appraisal of the potential role of FGFR3 in advanced urothelial carcinoma
Nan Sethakorn,Peter H. O'Donnell +1 more
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TLDR
It is argued that routine use of molecular genomic tumour analysis in UC may inform selection of patients for appropriate trials and the potential of FGFR3 as a meaningful clinical target for this difficult disease is investigated.Abstract:
Molecular analysis has identified subsets of urothelial carcinoma (UC) expressing distinct genetic signatures. Genomic alterations in the oncogenic fibroblast growth factor receptor 3 (FGFR3) pathway are among the most well described in UC and have led to extensive and ongoing investigation of FGFR3-targeted therapies in this disease, although no new drugs have yet been approved. Given the unmet need for effective treatments in advanced and metastatic UC, a better understanding of the known molecular alterations of FGFR3 and of the previous and ongoing clinical investigations of this promising target in UC deserves attention. The objective of the present review is to describe the landscape of alterations and biology of FGFR3 in UC, comprehensively summarize the current state of UC clinical trials of FGFR3 inhibitors, and discuss future therapeutic applications. Using the Pubmed and Clinicaltrials.gov databases, articles describing the spectrum and biological activity of FGFR3 genomic alterations and trials of FGFR3 inhibitors in UC were identified. Search terms included 'FGFR3 genomic alterations' and 'urothelial cancer' or 'bladder cancer'. Genomic alterations, including translocations and activating mutations, are increasingly described in advanced and metastatic UC. The majority of clinical trials have been performed in unselected populations; however, recent studies have reported encouraging preliminary data. We argue that routine use of molecular genomic tumour analysis in UC may inform selection of patients for appropriate trials and we further investigate the potential of FGFR3 as a meaningful clinical target for this difficult disease.read more
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Journal ArticleDOI
The evolving genomic landscape of urothelial carcinoma
TL;DR: The next generation of therapies for urothelial carcinoma will be based on patient-specific targetable mutations found in individual tumours, and has the potential to improve patient outcomes and survival.
Journal ArticleDOI
The evolution of bladder cancer genomics: What have we learned and how can we use it?
TL;DR: A new understanding of bladder cancer will optimistically translate into better understanding of this heterogeneous disease and lead to improvement in patient outcome and quality of life through better tailored treatments.
Journal ArticleDOI
Exome-Wide Association Study of Pancreatic Cancer Risk
Robert C. Grant,Robert E. Denroche,Ayelet Borgida,Carl Virtanen,Natalie Cook,Alyssa L. Smith,Ashton A. Connor,Julie M. Wilson,Gloria Peterson,Nicholas J. Roberts,Alison P. Klein,Sean M. Grimmond,Andrew V. Biankin,Andrew V. Biankin,Andrew V. Biankin,Sean P. Cleary,Malcolm A.S. Moore,Mathieu Lemire,George Zogopoulos,Lincoln Stein,Steven Gallinger +20 more
TL;DR: A case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreaticcancer and also identified candidate pancreatic cancers genes.
Journal ArticleDOI
Prospects and progress of immunotherapy for bladder cancer.
Martin Boegemann,Ahmet M. Aydin,Ahmet M. Aydin,Aditya Bagrodia,Laura Maria Krabbe,Laura Maria Krabbe +5 more
TL;DR: An overview of the history and rationale for immunotherapy in bladder cancer and the currently available data evaluating checkpoint inhibitors for bladder cancer are provided, and ongoing trials and future perspectives for urothelial carcinoma treatment are discussed.
Journal ArticleDOI
Fibroblast growth factor receptor 3 (FGFR3) aberrations in muscle-invasive urothelial carcinoma.
TL;DR: Patients with FGFR3 mutations orFGFR3-TACC3 fusion may constitute potential candidates for a novel FGFR-targeted therapy in the perioperative setting in Korean patients with UC.
References
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Cancer drug resistance: an evolving paradigm
TL;DR: There are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.
Journal ArticleDOI
Comprehensive molecular characterization of urothelial bladder carcinoma
John N. Weinstein,Rehan Akbani,Bradley M. Broom,Wenyi Wang,Roeland Verhaak,David J. McConkey,Seth P. Lerner,Margaret Morgan,Chad J. Creighton,Carolyn L. Smith,Andrew D. Cherniack,Jaegil Kim,Chandra Sekhar Pedamallu,Michael S. Noble,Hikmat Al-Ahmadie,Victor E. Reuter,Jonathan E. Rosenberg,Dean F. Bajorin,Bernard H. Bochner,David B. Solit,Theresa M. Koppie,Brian D. Robinson,Dmitry A. Gordenin,David C. Fargo,Leszek J. Klimczak,Steven A. Roberts,Jessie Au,Peter W. Laird,Toshinori Hinoue,Nikolaus Schultz,Ricardo Ramirez,Donna E. Hansel,Katherine A. Hoadley,William Y. Kim,Jeffrey S. Damrauer,Stephen B. Baylin,Andrew J. Mungall,A. Gordon Robertson,Andy Chu,David J. Kwiatkowski,Carrie Sougnez,Kristian Cibulskis,Lee Lichtenstein,Andrey Sivachenko,Chip Stewart,Michael S. Lawrence,Gad Getz,Eric S. Lander,Stacey B. Gabrie,Lawrence A. Donehower,Scott L. Carter,Gordon Saksena,Steven E. Schumacher,Samuel S. Freeman,Joonil Jung,Ami S. Bhatt,Trevor J. Pugh,Rameen Beroukhim,Matthew Meyerson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Noreen Dhalla,Carrie Hirst,Robert A. Holt,Steven J.M. Jones,Darlene Lee,Haiyan I. Li,Marco A. Marra,Michael Mayo,Richard A. Moore,Jacqueline E. Schein,Payal Sipahimalani,Angela Tam,Nina Thiessen,Tina Wong,Natasja Wye,Reanne Bowlby,Eric Chuah,Ranabir Guin,Hui Shen,Moiz S. Bootwalla,Timothy J. Triche,Phillip H. Lai,David Van Den Berg,Daniel J. Weisenberger,Saianand Balu,Tom Bodenheimer,Alan P. Hoyle,Stuart R. Jefferys,Shaowu Meng,Lisle E. Mose,Janae V. Simons,Mathew G. Soloway,Junyuan Wu,Joel S. Parker,D. Neil Hayes,Jeffrey Roach,Elizabeth Buda,Corbin D. Jones,Piotr A. Mieczkowski,Donghui Tan,Umadevi Veluvolu,Scot Waring,J. Todd Auman,Charles M. Perou,Matthew D. Wilkerson,Netty Santoso,Michael Parfenov,Xiaojia Ren,Angeliki Pantazi,Angela Hadjipanayis,Jonathan G. Seidman,Raju Kucherlapati,Semin Lee,Lixing Yang,Peter J. Park,Andrew Wei Xu,Alexei Protopopov,Jianhua Zhang,Christopher A. Bristow,Harshad S. Mahadeshwar,Sahil Seth,Xingzhi Song,Jiabin Tang,Dong Zeng,Lynda Chin,Lynda Chin,Charles C. Guo,Tod D. Casasent,Wenbin Liu,Zhenlin Ju,Thomas C. Motter,Bo Peng,Michael Ryan,Xiaoping Su,Ji Yeon Yang,Philip L. Lorenzi,Hui Yao,Nianxiang Zhang,Jiexin Zhang,Gordon B. Mills,Juok Cho,Daniel DiCara,Scott Frazer,Nils Gehlenborg,David I. Heiman,Pei Lin,Yingchun Liu,Petar Stojanov,Doug Voet,Hailei Zhang,Lihua Zou,Brady Bernard,Dick Kreisberg,Sheila Reynolds,Hector Rovira,Ilya Shmulevich,Jianjiong Gao,Anders Jacobsen,B. Arman Aksoy,Yevgeniy Antipin,Giovanni Ciriello,Gideon Dresdner,Benjamin Gross,William Lee,Boris Reva,Ronglai Shen,Rileen Sinha,S. Onur Sumer,Nils Weinhold,Marc Ladanyi,Chris Sander,Christopher C. Benz,Daniel E. Carlin,David Haussler,Sam Ng,Evano Paull,Joshua M. Stuart,Jing Zhu,Yuexin Liu,Wei Zhang,Barry S. Taylor,Tara M. Lichtenberg,Erik Zmuda,Thomas Barr,Aaron D. Black,Myra M. George,Benjamin Hanf,Carmen Helsel,Cynthia McAllister,Nilsa C. Ramirez,Nilsa C. Ramirez,Teresa R. Tabler,Stephanie Weaver,Lisa Wise,Jay Bowen,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Weiguo Jian,Sebrina A Tello,Michael Ittman,Patricia Castro,Whitney D. McClenden,Richard A. Gibbs,Charles Saller,Katherine Tarvin,Jennifer DiPiero,Jennifer Owens,Roni J. Bollag,Qiang Li,Paul M. Weinberger,Christine Czerwinski,Lori Huelsenbeck-Dill,Mary Iacocca,Nicholas J. Petrelli,Brenda Rabeno,Pat Swanson,Troy Shelton,Erin Curley,Johanna Gardner,David Mallery,Robert Penny,Nguyen Van Bang,Phan Thi Hanh,Bernard Kohl,Xuan Van Le,Bui Duc Phu,Richard Thorp,Nguyen Viet Tien,Le Quang Vinh,George E. Sandusky,Eric J. Burks,Kimberly R. Christ,Jason R. Gee,Antonia H. Holway,Alireza Moinzadeh,Andrea Sorcini,Travis Sullivan,Ilana Rebecca Garcia-Grossman,Ashley Marie Regazzi,Lori Boice,W.K. Rathmell,Leigh B. Thorne,Sheldon I. Bastacky,Benjamin Davies,Rajiv Dhir,Jeffrey R. Gingrich,Ronald L. Hrebinko,Jodi K. Maranchie,Joel B. Nelson,Anil V. Parwani,Wiam Bshara,Carmelo Gaudioso,Carl Morrison,Vina Alexopoulou,John M. S. Bartlett,Jay Engel,Sugy Kodeeswaran,Tatjana Antic,Peter H. O'Donnell,Norm D. Smith,Gary D. Steinberg,Sophie C. Egea,Carmen Gomez-Fernandez,Lynn M. Herbert,Merce Jorda,Mark S. Soloway,Allison Beaver,Suzie Carter,Payal Kapur,Cheryl M. Lewis,Yair Lotan,Jolanta Bondaruk,Bogdan Czerniak,Eila C. Skinner,Kenneth Aldape,Mark A. Jensen,Ari B. Kahn,Todd Pihl,David Pot,Deepak Srinivasan,Yunhu Wan,Martin L. Ferguson,Jean C. Zenklusen,Tanja Davidsen,John A. Demchok,Kenna R. Mills Shaw,Kenna R. Mills Shaw,Margi Sheth,Roy Tarnuzzer,Zhining Wang,Liming Yang,Carolyn M. Hutter,Bradley A. Ozenberger,Heidi J. Sofia,Greg Eley +296 more
TL;DR: Ch Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
Journal ArticleDOI
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
Thomas Powles,Joseph Paul Eder,Gregg Fine,Fadi Braiteh,Yohann Loriot,Cristina Cruz,Joaquim Bellmunt,Howard A. Burris,Daniel P. Petrylak,Siew-leng Melinda Teng,Xiaodong Shen,Zachary Boyd,Priti S. Hegde,Daniel S. Chen,Nicholas J. Vogelzang +14 more
TL;DR: It is demonstrated that tumours expressing PD-L1-positive tumour-infiltrating immune cells had particularly high response rates, and patients with UBC, who are often older and have a higher incidence of renal impairment, may be better able to tolerate MPDL3280A versus chemotherapy.
Journal ArticleDOI
Identification of Distinct Basal and Luminal Subtypes of Muscle-Invasive Bladder Cancer with Different Sensitivities to Frontline Chemotherapy
Woonyoung Choi,Sima P. Porten,Seungchan Kim,Daniel L. Willis,Elizabeth R. Plimack,Jean H. Hoffman-Censits,Beat Roth,Tiewei Cheng,Mai Tran,Mai Tran,I-Ling Lee,Jonathan Melquist,Jolanta Bondaruk,Tadeusz Majewski,Shizhen Zhang,Shanna Pretzsch,Keith A. Baggerly,Arlene O. Siefker-Radtke,Bogdan Czerniak,Colin P.N. Dinney,David J. McConkey,David J. McConkey +21 more
TL;DR: P53-like MIBCs were consistently resistant to neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and all chemoresistant tumors adopted a p53- like phenotype after therapy.
Journal ArticleDOI
Molecular biology of bladder cancer: new insights into pathogenesis and clinical diversity
TL;DR: Improved understanding of molecular features, disease pathogenesis and heterogeneity provides new opportunities for prognostic application, disease monitoring and personalized therapy in urothelial cancer.
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