Journal ArticleDOI
Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial.
Stephanie Lheureux,Mihaela C. Cristea,Jeff Bruce,Swati Garg,Michael Cabanero,Gina Mantia-Smaldone,Alexander B. Olawaiye,Susan Ellard,Johanne I Weberpals,Andrea E. Wahner Hendrickson,Gini F. Fleming,Stephen Welch,Neesha C. Dhani,Tracy Stockley,Prisni Rath,Katherine Karakasis,Gemma N Jones,Suzanne Jenkins,Jaime Rodriguez-Canales,Michael Tracy,Qian Tan,Valerie Bowering,Smitha Udagani,Lisa Wang,Charles A. Kunos,Eric Chen,Trevor J. Pugh,Amit M. Oza +27 more
TLDR
In this paper, the Wee1 inhibitor combined with gemcitabine was evaluated in patients with high-grade serous ovarian cancer, a TP53-mutated tumour type with high replication stress.About:
This article is published in The Lancet.The article was published on 2021-01-23. It has received 98 citations till now. The article focuses on the topics: Gemcitabine & Cancer.read more
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Cancer of the ovary, fallopian tube, and peritoneum: 2021 update.
Jonathan S. Berek,Malte Renz,Sean Kehoe,Sean Kehoe,Lalit Kumar,Michael Friedlander,Michael Friedlander +6 more
TL;DR: The FIGO's Committee for Gynecologic Oncology revised the staging of ovarian cancer, incorporating ovarian, fallopian tube, and peritoneal cancer into the same system as mentioned in this paper.
Journal ArticleDOI
Targeting replication stress in cancer therapy
Alexandre André B A da Costa,Dipanjan Chowdhury,B. Shapiro,Alan D. D'Andrea,Panagiotis A. Konstantinopoulos +4 more
TL;DR: Current and emerging approaches for targeting replication stress in cancer, from preclinical and biomarker development to clinical trial evaluation are reviewed.
Journal ArticleDOI
Inhibition of WEE1 Is Effective in TP53- and RAS-Mutant Metastatic Colorectal Cancer: A Randomized Trial (FOCUS4-C) Comparing Adavosertib (AZD1775) With Active Monitoring
J. Seligmann,David Fisher,Louise Brown,Richard Adams,Janet Graham,Philip Quirke,S. Richman,Rachel Butler,Enric Domingo,Andrew Blake,Michael Braun,F. Collinson,Robert H. Jones,Ewan Brown,E. De Winton,T. Humphies,Richard Kaplan,R. J. Wilson,Matthew T. Seymour,Tim Maughan +19 more
TL;DR: Adavosertib as mentioned in this paper is the first small-molecule inhibitor of WEE1 kinase, which has shown promising results in RAS-mutant metastatic colorectal cancer.
Journal ArticleDOI
Targeting the replication stress response through synthetic lethal strategies in cancer medicine.
TL;DR: The replication stress response (RSR) involves a downstream kinase cascade comprising ataxia telangiectasia-mutated (ATM), ATM and rad3-related (ATR), checkpoint kinases 1 and 2 (CHK1/2), and WEE1-like protein kinase (WEE1) which cooperate to arrest the cell cycle, protect stalled forks, and allow time for replication fork repair.
Journal ArticleDOI
Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study
TL;DR: In this paper , the efficacy, safety, and pharmacokinetics of adavosertib in combination with four chemotherapy agents commonly used in patients with primary platinum-resistant ovarian cancer were evaluated.
References
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Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
Freddie Bray,Jacques Ferlay,Isabelle Soerjomataram,Rebecca L. Siegel,Lindsey A. Torre,Ahmedin Jemal +5 more
TL;DR: A status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions.
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Integrated genomic analyses of ovarian carcinoma
Debra A. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,M. Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Beth Y. Karlan,Douglas A. Levine,Douglas A. Levine,Douglas A. Levine,Gordon B. Mills,Gordon B. Mills,Carl Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,J. A. Drummond,G. Fowler,Preethi H. Gunaratne,A. C. Hawes,C. L. Kovar,L. R. Lewis,M. B. Morgan,I. F. Newsham,J. Santibanez,Jeffrey G. Reid,L. R. Trevino,Yue Wu,M. Wang,Donna M. Muzny,D. A. Wheeler,Richard A. Gibbs,Gad Getz,Gad Getz,Michael S. Lawrence,Michael S. Lawrence,Kristian Cibulskis,Kristian Cibulskis,Andrey Sivachenko,C. Sougnez,Douglas Voet,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,Kristin G. Ardlie,T. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,M. O'Laughlin,D. J. Dooling,Linnea Fulton,R. Abbott,N. D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Hayden R. Schmidt,Joelle Kalicki,K. D. Delehaunty,Catrina Fronick,Ryan Demeter,L. Cook,J. W. Wallis,L. Lin,Vincent Magrini,J. S. Hodges,James M. Eldred,S. M. Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,R. G.W. Verhaak,Suzie Carter,Craig H. Mermel,G. Saksena,G. Saksena,H. Nguyen,R. C. Onofrio,D. Hubbard,S. Gupta,A. Crenshaw,A. H. Ramos,Lynda Chin,Lynda Chin,Alexei Protopopov,Jinghui Zhang,Jinghui Zhang,Jinghui Zhang,T. M. Kim,Ilana Perna,Y. Xiao,Hailei Zhang,Gang Ren,N. Sathiamoorthy,R. W. Park,R. W. Park,Eunjung Lee,Peter J. Park,Peter J. Park,Raju Kucherlapati,D. M. Absher,L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,L. Cope,James G. Herman,H. Shen,Daniel J. Weisenberger,Houtan Noushmehr,F. Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,J. Buckley,Stephen B. Baylin,Paul T. Spellman,Paul T. Spellman,Elizabeth Purdom,Pierre Neuvial,Pierre Neuvial,Henrik Bengtsson,Henrik Bengtsson,L. R. Jakkula,S. Durinck,S. Durinck,Junhong Han,Junhong Han,S. Dorton,H. Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,J. G. Conboy,Bahram Parvin,H. S. Feiler,Terence P. Speed,Joe W. Gray,Joe W. Gray,N. D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Nikolaus Schultz,L. Borsu,Alex E. Lash,Cameron Brennan,A. Viale,Chris Sander,M. Ladanyi,M. Ladanyi,Katherine A. Hoadley,Katherine A. Hoadley,S. Meng,Y. Du,Y. Du,Yigong Shi,Lulin Li,Y. J. Turman,D. Zang,E. B. Helms,S. Balu,Xiang Zhou,Jane Y. Wu,M. D. Topal,D. N. Hayes,D. N. Hayes,Charles M. Perou,Chaowei Wu,S. Shukla,A. Sivachenko,R. Jing,Yingkai Liu,M. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,A. Olshen,B. Reva,Yevgeniy Antipin,R. Shen,P. Mankoo,Robert L. Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Z. Sanborn,Charles J. Vaske,Jieqing Zhu,Christopher Szeto,G. K. Scott,Christina Yau,Matthew D. Wilkerson,N. Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,T. Shelton,Dirk Grimm,Martha Hatfield,Scott Morris,P. Yena,P. Rhodes,Mark E. Sherman,J. Paulauskis,S. Millis,A. Kahn,John M. Greene,R. Sfeir,M. A. Jensen,John W. Chen,J. Whitmore,S. Alonso,J. Jordan,A. Chu,A. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jane Peterson,Elizabeth J. Thomson +285 more
TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Journal ArticleDOI
Whole-genome characterization of chemoresistant ovarian cancer
Ann-Marie Patch,Ann-Marie Patch,Elizabeth L. Christie,Dariush Etemadmoghadam,Dariush Etemadmoghadam,Dale W. Garsed,Joshy George,Sian Fereday,Katia Nones,Katia Nones,Prue A. Cowin,Kathryn Alsop,Peter Bailey,Peter Bailey,Karin S. Kassahn,Karin S. Kassahn,Felicity Newell,Michael C.J. Quinn,Michael C.J. Quinn,Stephen H. Kazakoff,Stephen H. Kazakoff,Kelly Quek,Charlotte Wilhelm-Benartzi,Edward Curry,Huei San Leong,Anne Hamilton,Anne Hamilton,Anne Hamilton,Linda Mileshkin,George Au-Yeung,Catherine Kennedy,Jillian Hung,Yoke Eng Chiew,Paul R. Harnett,Michael Friedlander,Michael C. J. Quinn,Jan Pyman,Stephen Cordner,Patricia C. M. O’Brien,Jodie Leditschke,Greg Young,Kate Strachan,Paul Waring,Walid J Azar,Chris Mitchell,Nadia Traficante,Joy Hendley,Heather Thorne,Mark Shackleton,David Miller,Gisela Mir Arnau,Richard W. Tothill,Timothy P. Holloway,Timothy Semple,Ivon Harliwong,Craig Nourse,Ehsan Nourbakhsh,Suzanne Manning,Senel Idrisoglu,Timothy J. C. Bruxner,Angelika N. Christ,Barsha Poudel,Oliver Holmes,Oliver Holmes,Matthew J. Anderson,Conrad Leonard,Conrad Leonard,Andrew Lonie,Nathan E. Hall,Scott Wood,Scott Wood,Darrin Taylor,Qinying Xu,Qinying Xu,J. Lynn Fink,Nick Waddell,Ronny Drapkin,Euan A. Stronach,Hani Gabra,Robert S. Brown,A. Jewell,Shivashankar H. Nagaraj,Emma Markham,Peter Wilson,Jason Ellul,Orla McNally,Maria A. Doyle,Ravikiran Vedururu,Collin Stewart,Ernst Lengyel,John V. Pearson,John V. Pearson,Nicola Waddell,Nicola Waddell,Anna deFazio,Sean M. Grimmond,Sean M. Grimmond,David D.L. Bowtell,David D.L. Bowtell,David D.L. Bowtell +99 more
TL;DR: It is shown that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance.
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Regulation of DNA repair throughout the cell cycle
Dana Branzei,Marco Foiani +1 more
TL;DR: The repair of DNA lesions that occur endogenously or in response to diverse genotoxic stresses is indispensable for genome integrity and has provided insights into the mechanisms that contribute to DNA repair in specific cell-cycle phases.
Journal ArticleDOI
Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
Antonio González-Martín,Bhavana Pothuri,Ignace Vergote,René dePont Christensen,Whitney Graybill,Mansoor Raza Mirza,C McCormick,Domenica Lorusso,Paul Hoskins,Gilles Freyer,Klaus Baumann,K. Jardon,Andrés Redondo,Richard G. Moore,Christof Vulsteke,Roisin E. O'Cearbhaill,Bente Lund,Floor J. Backes,Pilar Barretina-Ginesta,Ashley Haggerty,Maria J. Rubio-Pérez,Mark S. Shahin,Giorgia Mangili,William H. Bradley,Ilan Bruchim,Kaiming Sun,I Malinowska,Y. Li,Divya Gupta,Bradley J. Monk,Engot-Ov,Gog Investigators +31 more
TL;DR: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival thanThose who received placebo, regardless of the presence or absence of homologous-recombination deficiency.
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