Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors
Antje Neeb,Nicolás Herranz,Sara Arce-Gallego,Susana Miranda,Lorenzo Buroni,Wei Yuan,Alejandro Athie,Teresa Casals,J. Carmichael,J. Carmichael,Daniel Nava Rodrigues,Bora Gurel,Pasquale Rescigno,Pasquale Rescigno,Jan Rekowski,Jon Welti,Ruth Riisnaes,Veronica Gil,Jian Ning,Verena Wagner,Irene Casanova-Salas,Sarai Cordoba,Natalia Castro,Maria de Los Dolores Fenor de la Maza,Maria de Los Dolores Fenor de la Maza,George Seed,Khobe Chandran,Khobe Chandran,Ana Ferreira,Ines Figueiredo,Claudia Bertan,Diletta Bianchini,Diletta Bianchini,Caterina Aversa,Caterina Aversa,Alec Paschalis,Alec Paschalis,Macarena Gonzalez,Rafael Morales-Barrera,Cristina Suarez,Joan Carles,Amanda Swain,Adam Sharp,Adam Sharp,Jesús Gil,Violeta Serra,Christopher J. Lord,Suzanne Carreira,Joaquin Mateo,Johann S. de Bono,Johann S. de Bono +50 more
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TLDR
This data indicates that ATM loss in PC is not always detected by targeted NGS, associates with genomic instability, and is most sensitive to combined ATR and PARP inhibition.About:
This article is published in European Urology.The article was published on 2021-02-01 and is currently open access. It has received 63 citations till now.read more
Citations
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Journal ArticleDOI
Talazoparib monotherapy in metastatic castration-resistant prostate cancer with DNA repair alterations (TALAPRO-1): an open-label, phase 2 trial
Johann S. de Bono,Niven Mehra,Giorgio V. Scagliotti,Elena Castro,Tanya B. Dorff,A. Stirling,Arnulf Stenzl,Mark D. Fleming,Celestia S. Higano,Fred Saad,Consuelo Buttigliero,Inge M. van Oort,A. Douglas Laird,Marielena Mata,Hsiang-Chun Chen,Cynthia G. Healy,Akos Czibere,Karim Fizazi +17 more
TL;DR: In this paper, the authors assessed the PARP inhibitor talazoparib in metastatic castration-resistant prostate cancers with DNA damage response (DDR) alterations in genes involved directly or indirectly in homologous recombination repair (HRR).
Journal ArticleDOI
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial.
Suzanne Carreira,Nuria Porta,Sara Arce-Gallego,George Seed,Alba Llop-Guevara,Diletta Bianchini,Diletta Bianchini,Pasquale Rescigno,Pasquale Rescigno,Alec Paschalis,Alec Paschalis,Claudia Bertan,Chloe Baker,Jane Goodall,Susana Miranda,Ruth Riisnaes,Ines Figueiredo,Ana Ferreira,Rita Pereira,Mateus Crespo,Bora Gurel,Daniel Nava Rodrigues,Stephen J. Pettitt,Wei Yuan,Violeta Serra,Jan Rekowski,Christopher J. Lord,Emma Hall,Joaquin Mateo,Joaquin Mateo,Joaquin Mateo,Johann S. de Bono,Johann S. de Bono +32 more
TL;DR: In this article, the authors analyzed TOPARP-B phase II clinical trial samples, evaluating whole-exome and low-pass whole-genome sequencing and IHC and IF assays evaluating ATM and RAD51 foci (testing homologous recombination repair function).
Journal ArticleDOI
Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021.
Silke Gillessen,Andrew J. Armstrong,Gerhardt Attard,Tomasz M. Beer,Himisha Beltran,Anders Bjartell,Alberto Bossi,Alberto Briganti,Robert G. Bristow,Muhammad Bulbul,Orazio Caffo,Kim N. Chi,Caroline S. Clarke,Noel W. Clarke,Ian D. Davis,Johann S. de Bono,Ignacio Duran,Rosalind A. Eeles,Eleni Efstathiou,Jason A. Efstathiou,O. Ekeke,Christopher H. Evans,Stefano Fanti,Felix Y. Feng,Karim Fizazi,Mark Frydenberg,Daniel J. George,Martin E. Gleave,Susan Halabi,D. Heinrich,C. Higano,Michael S Hofman,Maha Hussain,Nicholas D. James,Robert Jones,Ravindran Kanesvaran,Raja B. Khauli,Laurence Klotz,Raya Leibowitz,Christopher J. Logothetis,Fernando C. Maluf,Robin Millman,Alicia K. Morgans,Michael J. Morris,Nicolas Mottet,Hind Mrabti,Declan G. Murphy,Vedang Murthy,William Oh,Piet Ost,Joe M. O'Sullivan,Anwar R. Padhani,Chris Parker,Darren M.C. Poon,Colin C. Pritchard,Danny M. Rabah,Dana E. Rathkopf,Robert E. Reiter,M.L. Rubin,Charles J. Ryan,Fred Saad,Juan Pablo Sade,Oliver Sartor,Howard I. Scher,Neal D. Shore,Iwona Skoneczna,Eric J. Small,Matthew R. Smith,Howard R. Soule,Daniel E. Spratt,Cora N. Sternberg,H. Suzuki,Christopher Sweeney,Matthew R. Sydes,Mary-Ellen Taplin,Derya Tilki,Bertrand Tombal,Levent Türkeri,Hiroji Uemura,Hirotsugu Uemura,Inge M. van Oort,Kosj Yamoah,Dingwei Ye,Almudena Zapatero,Aurelius Omlin +84 more
TL;DR: The 2019 Advanced Prostate Cancer Consensus Conference (APCCC) as mentioned in this paper addressed three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood.
Journal ArticleDOI
The treatment landscape of metastatic prostate cancer.
Yasutaka Yamada,Himisha Beltran +1 more
TL;DR: In this article, the authors discuss the current treatment landscape of metastatic prostate cancer, clinical challenges, and the emerging role of molecular biomarkers for targeting biologic subsets of advanced disease and co-targeting heterogenous resistance patterns.
Journal ArticleDOI
Cell Cycle Checkpoints and Beyond: Exploiting the ATR/CHK1/WEE1 Pathway for the Treatment of PARP Inhibitor-Resistant Cancer.
TL;DR: In this paper , the authors discuss the cell cycle checkpoints and their roles beyond mere cell cycle regulation as part of the arsenal to overcome PARPi-resistant cancers, and address the current status and recent advancements as well as limitations of cell cycle checkpoint inhibitors in clinical trials.
References
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Journal ArticleDOI
Integrative clinical genomics of advanced prostate cancer
Dan R. Robinson,Eliezer M. Van Allen,Eliezer M. Van Allen,Yi-Mi Wu,Nikolaus Schultz,Robert J. Lonigro,Juan Miguel Mosquera,Bruce Montgomery,Mary-Ellen Taplin,Colin C. Pritchard,Gerhardt Attard,Gerhardt Attard,Himisha Beltran,Wassim Abida,Robert K. Bradley,Jake Vinson,Xuhong Cao,Pankaj Vats,Lakshmi P. Kunju,Maha Hussain,Felix Y. Feng,Scott A. Tomlins,Kathleen A. Cooney,David Smith,Christine Brennan,Javed Siddiqui,Rohit Mehra,Yu Chen,Yu Chen,Dana E. Rathkopf,Dana E. Rathkopf,Michael J. Morris,Michael J. Morris,Stephen B. Solomon,Jeremy C. Durack,Victor E. Reuter,Anuradha Gopalan,Jianjiong Gao,Massimo Loda,Rosina T. Lis,Michaela Bowden,Michaela Bowden,Stephen P. Balk,Glenn C. Gaviola,Carrie Sougnez,Manaswi Gupta,Evan Y. Yu,Elahe A. Mostaghel,Heather H. Cheng,Hyojeong Mulcahy,Lawrence D. True,Stephen R. Plymate,Heidi Dvinge,Roberta Ferraldeschi,Roberta Ferraldeschi,Penny Flohr,Penny Flohr,Susana Miranda,Susana Miranda,Zafeiris Zafeiriou,Zafeiris Zafeiriou,Nina Tunariu,Nina Tunariu,Joaquin Mateo,Joaquin Mateo,Raquel Perez-Lopez,Raquel Perez-Lopez,Francesca Demichelis,Francesca Demichelis,Brian D. Robinson,Marc H. Schiffman,David M. Nanus,Scott T. Tagawa,Alexandros Sigaras,Kenneth Eng,Olivier Elemento,Andrea Sboner,Elisabeth I. Heath,Howard I. Scher,Howard I. Scher,Kenneth J. Pienta,Philip W. Kantoff,Johann S. de Bono,Johann S. de Bono,Mark A. Rubin,Peter S. Nelson,Levi A. Garraway,Levi A. Garraway,Charles L. Sawyers,Arul M. Chinnaiyan +89 more
TL;DR: This cohort study provides clinically actionable information that could impact treatment decisions for affected individuals and identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF.
Journal ArticleDOI
ATM and related protein kinases: safeguarding genome integrity
TL;DR: Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
Journal ArticleDOI
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
Joaquin Mateo,Suzanne Carreira,Shahneen Sandhu,Susana Miranda,Helen Mossop,Raquel Perez-Lopez,Daniel Nava Rodrigues,Dan R. Robinson,Aurelius Omlin,Nina Tunariu,Gunther Boysen,Nuria Porta,Penny Flohr,Alexa Gillman,Ines Figueiredo,Claire Paulding,George Seed,Suneil Jain,Christy Ralph,Andrew Protheroe,Syed A. Hussain,Robert Jones,Tony Elliott,Ursula McGovern,Diletta Bianchini,Jane C. Goodall,Zafeiris Zafeiriou,Chris T. Williamson,Roberta Ferraldeschi,Ruth Riisnaes,Bernardette Ebbs,Gemma Fowler,Desamparados Roda,Wei Yuan,Yi-Mi Wu,Xuhong Cao,Rachel Brough,Helen Pemberton,Roger A'Hern,Amanda Swain,Lakshmi P. Kunju,Rosalind A. Eeles,Gerhardt Attard,Christopher J. Lord,Alan Ashworth,Mark A. Rubin,Karen E. Knudsen,Felix Y. Feng,Arul M. Chinnaiyan,Emma Hall,Johann S. de Bono +50 more
TL;DR: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate.
Journal ArticleDOI
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors
Junko Murai,Shar Yin N. Huang,Benu Brata Das,Amelie Renaud,Yiping Zhang,James H. Doroshow,Jiuping Ji,Shunichi Takeda,Yves Pommier +8 more
TL;DR: This study shows that PARP inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA, providing a new mechanistic foundation for the rational application ofPARP inhibitors in cancer therapy.
Journal ArticleDOI
Causes and consequences of replication stress.
TL;DR: In this paper, the kinase ATR (ATM- and Rad3-related) stabilizes and helps to restart stalled replication forks, avoiding the generation of DNA damage and genome instability.
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