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1 September 2017
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PARP inhibitors (PARPi) have demonstrated activity in patients with mutations in homologous recombination (HR) genes such as BRCA1 and BRCA2 Three related studies identified HR gene reversion mutations that confer resistance to PARPi Kondrashova and colleagues discovered secondary reversion mutations in BRCA1, RAD51C, and RAD51D in patients with PARPi-resistant ovarian cancer Similarly, Quigley, Alumkal, and colleagues identified BRCA2 reversion mutations associated with PARPi resistance in circulating cell-free DNA (cfDNA) from two patients with prostate cancer Finally, Goodall, Mateo, and colleagues found secondary reversion mutations in BRCA2 and PALB2 in cfDNA from patients with PARPi-resistant metastatic prostate cancer Together, these studies demonstrate that HR gene reversion mutations can promote resistance to PARPi For details, please see the article by Kondrashova and colleagues on page 984, the article by Quigley, Alumkal, and colleagues on page 999, and the article by Goodall, Mateo, and colleagues on page 1006. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Review
Research Briefs
Author Choice
A Next-Generation TRK Kinase Inhibitor Overcomes Acquired Resistance to Prior TRK Kinase Inhibition in Patients with TRK Fusion–Positive Solid Tumors
Alexander Drilon; Ramamoorthy Nagasubramanian; James F. Blake; Nora Ku; Brian B. Tuch; Kevin Ebata; Steve Smith; Veronique Lauriault; Gabrielle R. Kolakowski; Barbara J. Brandhuber; Paul D. Larsen; Karyn S. Bouhana; Shannon L. Winski; Robyn Hamor; Wen-I Wu; Andrew Parker; Tony H. Morales; Francis X. Sullivan; Walter E. DeWolf; Lance A. Wollenberg; Paul R. Gordon; Dorothea N. Douglas-Lindsay; Maurizio Scaltriti; Ryma Benayed; Sandeep Raj; Bethany Hanusch; Alison M. Schram; Philip Jonsson; Michael F. Berger; Jaclyn F. Hechtman; Barry S. Taylor; Steve Andrews; S. Michael Rothenberg; David M. Hyman
Exome Sequencing of African-American Prostate Cancer Reveals Loss-of-Function ERF Mutations
Franklin W. Huang; Juan Miguel Mosquera; Andrea Garofalo; Coyin Oh; Maria Baco; Ali Amin-Mansour; Bokang Rabasha; Samira Bahl; Stephanie A. Mullane; Brian D. Robinson; Saud Aldubayan; Francesca Khani; Beerinder Karir; Eejung Kim; Jeremy Chimene-Weiss; Matan Hofree; Alessandro Romanel; Joseph R. Osborne; Jong Wook Kim; Gissou Azabdaftari; Anna Woloszynska-Read; Karen Sfanos; Angelo M. De Marzo; Francesca Demichelis; Stacey Gabriel; Eliezer M. Van Allen; Jill Mesirov; Pablo Tamayo; Mark A. Rubin; Isaac J. Powell; Levi A. Garraway
Author Choice
Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Olga Kondrashova; Minh Nguyen; Kristy Shield-Artin; Anna V. Tinker; Nelson N.H. Teng; Maria I. Harrell; Michael J. Kuiper; Gwo-Yaw Ho; Holly Barker; Maria Jasin; Rohit Prakash; Elizabeth M. Kass; Meghan R. Sullivan; Gregory J. Brunette; Kara A. Bernstein; Robert L. Coleman; Anne Floquet; Michael Friedlander; Ganessan Kichenadasse; David M. O'Malley; Amit Oza; James Sun; Liliane Robillard; Lara Maloney; David Bowtell; on behalf of the AOCS Study Group; Heidi Giordano; Matthew J. Wakefield; Scott H. Kaufmann; Andrew D. Simmons; Thomas C. Harding; Mitch Raponi; Iain A. McNeish; Elizabeth M. Swisher; Kevin K. Lin; Clare L. Scott
Author Choice
Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors
David Quigley; Joshi J. Alumkal; Alexander W. Wyatt; Vishal Kothari; Adam Foye; Paul Lloyd; Rahul Aggarwal; Won Kim; Eric Lu; Jacob Schwartzman; Kevin Beja; Matti Annala; Rajdeep Das; Morgan Diolaiti; Colin Pritchard; George Thomas; Scott Tomlins; Karen Knudsen; Christopher J. Lord; Charles Ryan; Jack Youngren; Tomasz M. Beer; Alan Ashworth; Eric J. Small; Felix Y. Feng
Research Articles
Author Choice
Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition
Jane Goodall; for the TOPARP-A investigators; Joaquin Mateo; for the TOPARP-A investigators; Wei Yuan; for the TOPARP-A investigators; Helen Mossop; for the TOPARP-A investigators; Nuria Porta; for the TOPARP-A investigators; Susana Miranda; for the TOPARP-A investigators; Raquel Perez-Lopez; for the TOPARP-A investigators; David Dolling; for the TOPARP-A investigators; Dan R. Robinson; for the TOPARP-A investigators; Shahneen Sandhu; for the TOPARP-A investigators; Gemma Fowler; for the TOPARP-A investigators; Berni Ebbs; for the TOPARP-A investigators; Penny Flohr; for the TOPARP-A investigators; George Seed; for the TOPARP-A investigators; Daniel Nava Rodrigues; for the TOPARP-A investigators; Gunther Boysen; for the TOPARP-A investigators; Claudia Bertan; for the TOPARP-A investigators; Mark Atkin; for the TOPARP-A investigators; Matthew Clarke; for the TOPARP-A investigators; Mateus Crespo; for the TOPARP-A investigators; Ines Figueiredo; for the TOPARP-A investigators; Ruth Riisnaes; for the TOPARP-A investigators; Semini Sumanasuriya; for the TOPARP-A investigators; Pasquale Rescigno; for the TOPARP-A investigators; Zafeiris Zafeiriou; for the TOPARP-A investigators; Adam Sharp; for the TOPARP-A investigators; Nina Tunariu; for the TOPARP-A investigators; Diletta Bianchini; for the TOPARP-A investigators; Alexa Gillman; for the TOPARP-A investigators; Christopher J. Lord; for the TOPARP-A investigators; Emma Hall; for the TOPARP-A investigators; Arul M. Chinnaiyan; for the TOPARP-A investigators; Suzanne Carreira; for the TOPARP-A investigators; Johann S. de Bono; for the TOPARP-A investigators
Author Choice
Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma
Christian Grommes; Alessandro Pastore; Nicolaos Palaskas; Sarah S. Tang; Carl Campos; Derrek Schartz; Paolo Codega; Donna Nichol; Owen Clark; Wan-Ying Hsieh; Dan Rohle; Marc Rosenblum; Agnes Viale; Viviane S. Tabar; Cameron W. Brennan; Igor T. Gavrilovic; Thomas J. Kaley; Craig P. Nolan; Antonio Omuro; Elena Pentsova; Alissa A. Thomas; Elina Tsyvkin; Ariela Noy; M. Lia Palomba; Paul Hamlin; Craig S. Sauter; Craig H. Moskowitz; Julia Wolfe; Ahmet Dogan; Minhee Won; Jon Glass; Scott Peak; Enrico C. Lallana; Vaios Hatzoglou; Anne S. Reiner; Philip H. Gutin; Jason T. Huse; Katherine S. Panageas; Thomas G. Graeber; Nikolaus Schultz; Lisa M. DeAngelis; Ingo K. Mellinghoff
Discovery and Optimization of HKT288, a Cadherin-6–Targeting ADC for the Treatment of Ovarian and Renal Cancers
Carl U. Bialucha; Scott D. Collins; Xiao Li; Parmita Saxena; Xiamei Zhang; Clemens Dürr; Bruno Lafont; Pierric Prieur; Yeonju Shim; Rebecca Mosher; David Lee; Lance Ostrom; Tiancen Hu; Sanela Bilic; Ivana Liric Rajlic; Vladimir Capka; Wei Jiang; Joel P. Wagner; GiNell Elliott; Artur Veloso; Jessica C. Piel; Meghan M. Flaherty; Keith G. Mansfield; Emily K. Meseck; Tina Rubic-Schneider; Anne Serdakowski London; William R. Tschantz; Markus Kurz; Duc Nguyen; Aaron Bourret; Matthew J. Meyer; Jason E. Faris; Mary J. Janatpour; Vivien W. Chan; Nicholas C. Yoder; Kalli C. Catcott; Molly A. McShea; Xiuxia Sun; Hui Gao; Juliet Williams; Francesco Hofmann; Jeffrey A. Engelman; Seth A. Ettenberg; William R. Sellers; Emma Lees
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