Journal ArticleDOI
Treating cancer with selective CDK4/6 inhibitors
TLDR
Results of pivotal phase III trials investigating palbociclib in patients with advanced-stage oestrogen receptor (ER)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a well-tolerated toxicity profile.Abstract:
Uncontrolled cellular proliferation, mediated by dysregulation of the cell-cycle machinery and activation of cyclin-dependent kinases (CDKs) to promote cell-cycle progression, lies at the heart of cancer as a pathological process. Clinical implementation of first-generation, nonselective CDK inhibitors, designed to inhibit this proliferation, was originally hampered by the high risk of toxicity and lack of efficacy noted with these agents. The emergence of a new generation of selective CDK4/6 inhibitors, including ribociclib, abemaciclib and palbociclib, has enabled tumour types in which CDK4/6 has a pivotal role in the G1-to-S-phase cell-cycle transition to be targeted with improved effectiveness, and fewer adverse effects. Results of pivotal phase III trials investigating palbociclib in patients with advanced-stage oestrogen receptor (ER)-positive breast cancer have demonstrated a substantial improvement in progression-free survival, with a well-tolerated toxicity profile. Mechanisms of acquired resistance to CDK4/6 inhibitors are beginning to emerge that, although unwelcome, might enable rational post-CDK4/6 inhibitor therapeutic strategies to be identified. Extending the use of CDK4/6 inhibitors beyond ER-positive breast cancer is challenging, and will likely require biomarkers that are predictive of a response, and the use of combination therapies in order to optimize CDK4/6 targeting.read more
Citations
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The somatic genomic landscape of glioblastoma
Cameron Brennan,Roel G.W. Verhaak,Aaron McKenna,Benito Campos,Houtan Noushmehr,Sofie R. Salama,Siyuan Zheng,Debyani Chakravarty,J. Zachary Sanborn,Samuel H. Berman,Rameen Beroukhim,Brady Bernard,Chang-Jiun Wu,Giannicola Genovese,Ilya Shmulevich,Jill S. Barnholtz-Sloan,Lihua Zou,Rahulsimham Vegesna,Sachet A. Shukla,Giovanni Ciriello,W. K. Yung,Wei Zhang,Carrie Sougnez,Tom Mikkelsen,Kenneth Aldape,Darell D. Bigner,Erwin G. Van Meir,Michael D. Prados,Andrew E. Sloan,Keith L. Black,Jennifer M. Eschbacher,Gaetano Finocchiaro,William A. Friedman,David W. Andrews,Abhijit Guha,Mary Iacocca,Brian P. O'Neil,Greg Foltz,Jerome Myers,Daniel J. Weisenberger,Robert Penny,Raju Kucherlapati,Charles M. Perou,D. Neil Hayes,Richard A. Gibbs,Marco A. Marra,Gordon B. Mills,Eric S. Lander,Paul T. Spellman,Richard K. Wilson,Chris Sander,John N. Weinstein,Matthew Meyerson,Stacey Gabriel,Peter W. Laird,David Haussler,Gad Getz,Lynda Chin +57 more
TL;DR: In this article, the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs) was described, including several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA.
Journal ArticleDOI
Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer
Nicholas C. Turner,Dennis J. Slamon,Jungsil Ro,Igor Bondarenko,Seock-Ah Im,Norikazu Masuda,Marco Colleoni,Angela DeMichele,Sherene Loi,Sunil Verma,H. Iwata,Nadia Harbeck,Sibylle Loibl,Fabrice Andre,Kathy Puyana Theall,Xin Huang,Carla Giorgetti,Cynthia Huang Bartlett,Massimo Cristofanilli +18 more
TL;DR: Treating patients with hormone‐receptor–positive, HER2‐negative advanced breast cancer who had sensitivity to previous endocrine therapy with palbociclib plus fulvestrant resulted in longer overall survival than treatment with placebo–fulvestrant; the efficacy of subsequent therapies after disease progression; and safety.
Journal ArticleDOI
Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis.
Yixiao Feng,Yixiao Feng,Mia Spezia,Shifeng Huang,Shifeng Huang,Chengfu Yuan,Chengfu Yuan,Zongyue Zeng,Zongyue Zeng,Linghuan Zhang,Linghuan Zhang,Xiaojuan Ji,Xiaojuan Ji,Wei Liu,Wei Liu,Bo Huang,Bo Huang,Bo Huang,Wenping Luo,Wenping Luo,Bo Liu,Bo Liu,Yan Lei,Yan Lei,Scott Du,Akhila Vuppalapati,Hue H. Luu,Rex C. Haydon,Tong-Chuan He,Guosheng Ren +29 more
TL;DR: Emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer.
Journal ArticleDOI
Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies.
Yi-Zhou Jiang,Ding Ma,Chen Suo,Shi Jinxiu,Mengzhu Xue,Xin Hu,Yi Xiao,Ke Da Yu,Yi Rong Liu,Ying Yu,Yuanting Zheng,Xiangnan Li,Chen-Hui Zhang,Peng-Chen Hu,Jing Zhang,Qi Hua,Jiyang Zhang,Wanwan Hou,Luyao Ren,Ding Bao,B. Li,Jingcheng Yang,Ling Yao,Wen Jia Zuo,Shen Zhao,Yue Gong,Yi Xing Ren,Ya Xin Zhao,Yun Song Yang,Niu Zhenmin,Zhi Gang Cao,Daniel G. Stover,Claire F. Verschraegen,Virginia G. Kaklamani,Anneleen Daemen,John R. Benson,Kazuaki Takabe,Fan Bai,Da Qiang Li,Peng Wang,Leming Shi,Wei Huang,Zhi Ming Shao +42 more
TL;DR: The LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss than the other subtypes, and was classified as a mesenchymal-like subtype.
Journal ArticleDOI
Melanoma treatment in review.
TL;DR: This review aims to survey therapies approved and under evaluation for melanoma treatment and relevant research on the molecular mechanisms underlying melanomagenesis.
References
More filters
Journal ArticleDOI
Comprehensive molecular portraits of human breast tumours
Daniel C. Koboldt,Robert S. Fulton,Michael D. McLellan,Heather Schmidt,Joelle Kalicki-Veizer,Joshua F. McMichael,Lucinda Fulton,David J. Dooling,Li Ding,Elaine R. Mardis,Richard K. Wilson,Adrian Ally,Miruna Balasundaram,Yaron S.N. Butterfield,Rebecca Carlsen,Candace Carter,Andy Chu,Eric Chuah,Hye Jung E. Chun,Robin J.N. Coope,Noreen Dhalla,Ranabir Guin,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Jacqueline E. Schein,Arash Shafiei,Payal Sipahimalani,Jared R. Slobodan,Dominik Stoll,Angela Tam,Nina Thiessen,Richard Varhol,Natasja Wye,Thomas Zeng,Yongjun Zhao,Inanc Birol,Steven J.M. Jones,Marco A. Marra,Andrew D. Cherniack,Gordon Saksena,Gordon Saksena,Robert C. Onofrio,Nam H. Pho,Scott L. Carter,Steven E. Schumacher,Steven E. Schumacher,Barbara Tabak,Barbara Tabak,Bryan Hernandez,Jeff Gentry,Huy Nguyen,Andrew Crenshaw,Kristin G. Ardlie,Rameen Beroukhim,Rameen Beroukhim,Wendy Winckler,Gad Getz,Gad Getz,Stacey Gabriel,Matthew Meyerson,Matthew Meyerson,Lynda Chin,Lynda Chin,Raju Kucherlapati,Katherine A. Hoadley,J. Todd Auman,Cheng Fan,Yidi J. Turman,Yan Shi,Ling Li,Michael D. Topal,Xiaping He,Hann Hsiang Chao,Aleix Prat,Grace O. Silva,Michael D. Iglesia,Wei Zhao,Jerry Usary,Jonathan S. Berg,Michael C. Adams,Jessica K. Booker,Junyuan Wu,Anisha Gulabani,Tom Bodenheimer,Alan P. Hoyle,Janae V. Simons,Matthew G. Soloway,Lisle E. Mose,Stuart R. Jefferys,Saianand Balu,Joel S. Parker,D. Neil Hayes,Charles M. Perou,Simeen Malik,Swapna Mahurkar,Hui Shen,Daniel J. Weisenberger,Timothy J. Triche,Phillip H. Lai,Moiz S. Bootwalla,Dennis T. Maglinte,Benjamin P. Berman,David Van Den Berg,Stephen B. Baylin,Peter W. Laird,Chad J. Creighton,Lawrence A. Donehower,Michael S. Noble,Doug Voet,Nils Gehlenborg,Daniel Di Cara,Juinhua Zhang,Hailei Zhang,Chang-Jiun Wu,Spring Yingchun Liu,Michael S. Lawrence,Lihua Zou,Andrey Sivachenko,Pei Lin,Petar Stojanov,Rui Jing,Juok Cho,Raktim Sinha,Richard W. Park,Marc Danie Nazaire,James A. Robinson,Helga Thorvaldsdottir,Jill P. Mesirov,Peter J. Park,Sheila Reynolds,Richard Kreisberg,Brady Bernard,Ryan Bressler,Timo Erkkilä,Jake Lin,Vesteinn Thorsson,Wei Zhang,Ilya Shmulevich,Giovanni Ciriello,Nils Weinhold,Nikolaus Schultz,Jianjiong Gao,Ethan Cerami,Benjamin Gross,Anders Jacobsen,Rileen Sinha,B. Arman Aksoy,Yevgeniy Antipin,Boris Reva,Ronglai Shen,Barry S. Taylor,Marc Ladanyi,Chris Sander,Pavana Anur,Paul T. Spellman,Yiling Lu,Wenbin Liu,Roel R.G. Verhaak,Gordon B. Mills,Gordon B. Mills,Rehan Akbani,Nianxiang Zhang,Bradley M. Broom,Tod D. Casasent,Chris Wakefield,Anna K. Unruh,Keith A. Baggerly,Kevin R. Coombes,John N. Weinstein,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Evan O. Paull,Daniel E. Carlin,Christopher K. Wong,Artem Sokolov,Janita Thusberg,Sean D. Mooney,Sam Ng,Theodore C. Goldstein,Kyle Ellrott,Mia Grifford,Christopher Wilks,Singer Ma,Brian Craft,Chunhua Yan,Ying Hu,Daoud Meerzaman,Julie M. Gastier-Foster,Julie M. Gastier-Foster,Jay Bowen,Nilsa C. Ramirez,Nilsa C. Ramirez,Aaron D. Black,Robert E. Pyatt,Robert E. Pyatt,Peter White,Peter White,Erik Zmuda,Jessica Frick,Tara M. Lichtenberg,Robin Brookens,Myra M. George,Mark Gerken,Hollie A. Harper,Kristen M. Leraas,Lisa Wise,Teresa R. Tabler,Cynthia McAllister,Thomas Barr,Melissa Hart-Kothari,Katie Tarvin,Charles Saller,George E. Sandusky,Colleen Mitchell,Mary Iacocca,Jennifer Brown,Brenda Rabeno,Christine Czerwinski,Nicholas J. Petrelli,Oleg Dolzhansky,Mikhail Abramov,Olga Voronina,Olga Potapova,Jeffrey R. Marks,Wiktoria Maria Suchorska,Dawid Murawa,Witold Kycler,Matthew Ibbs,Konstanty Korski,Arkadiusz Spychała,Pawel Murawa,Jacek J. Brzeziński,Hanna Perz,Radoslaw Łaźniak,M. Teresiak,Honorata Tatka,Ewa Leporowska,Marta Bogusz-Czerniewicz,Julian Malicki,Andrzej Mackiewicz,Maciej Wiznerowicz,Xuan Van Le,Bernard Kohl,Nguyen Viet Tien,Richard Thorp,Nguyen Van Bang,Howard H. Sussman,Bui Duc Phu,Richard A. Hajek,Nguyen Phi Hung,Huynh Quyet Thang,Khurram Z. Khan,Robert Penny,David Mallery,Erin Curley,Candace Shelton,Peggy Yena,James N. Ingle,Fergus J. Couch,Wilma L. Lingle,Tari A. King,Ana M. Gonzalez-Angulo,Ana M. Gonzalez-Angulo,Mary D. Dyer,Shuying Liu,Xiaolong Meng,Modesto Patangan,Frederic Waldman,Frederic Waldman,Hubert Stoppler,W. Kimryn Rathmell,Leigh B. Thorne,Mei Huang,Lori Boice,Ashley Hill,Carl Morrison,Carmelo Gaudioso,Wiam Bshara,Kelly Daily,Sophie C. Egea,Mark D. Pegram,Carmen Gomez-Fernandez,Rajiv Dhir,Rohit Bhargava,Adam Brufsky,Craig D. Shriver,Jeffrey A. Hooke,Jamie Leigh Campbell,Richard J. Mural,Hai Hu,Stella Somiari,Caroline Larson,Brenda Deyarmin,Leonid Kvecher,Albert J. Kovatich,Matthew J. Ellis,Thomas Stricker,Kevin P. White,Olufunmilayo I. Olopade,Chunqing Luo,Yaqin Chen,Ron Bose,Li-Wei Chang,Andrew H. Beck,Todd Pihl,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Brenda Ayala,Mark Backus,Jessica Walton,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,David Pot,Margi Sheth,John A. Demchok,Kenna R. Mills Shaw,Liming Yang,Greg Eley,Martin L. Ferguson,Roy Tarnuzzer,Jiashan Zhang,Laura A.L. Dillon,Kenneth H. Buetow,Peter Fielding,Bradley A. Ozenberger,Mark S. Guyer,Heidi J. Sofia,Jacqueline D. Palchik +355 more
TL;DR: The ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity.
Journal ArticleDOI
CDK inhibitors: positive and negative regulators of G1-phase progression
TL;DR: This work challenges previous assumptions about how the G1/S transition of the mammalian cell cycle is governed, helps explain some enigmatic features of cell cycle control that also involve the functions of the retinoblastoma protein (Rb) and the INK4 proteins, and changes the thinking about how either p16 loss or overexpression of cyclin D-dependent kinases contribute to cancer.
Journal ArticleDOI
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
TL;DR: In this article, an improved two-hybrid system was employed to isolate human genes encoding Cdk-interacting proteins (Cips) and found that CIP1 is a potent, tight-binding inhibitor of Cdks and can inhibit the phosphorylation of Rb by cyclin A-Cdk2.
Journal ArticleDOI
Repeated observation of breast tumor subtypes in independent gene expression data sets
Therese Sørlie,Robert Tibshirani,Joel S. Parker,Trevor Hastie,James Stephen Marron,Andrew B. Nobel,Shibing Deng,Hilde Johnsen,Robert Pesich,Stephanie Geisler,Janos Demeter,Charles M. Perou,Per Eystein Lønning,Patrick O. Brown,Anne Lise Børresen-Dale,David Botstein +15 more
TL;DR: The results strongly support the idea that many of these breast tumor subtypes represent biologically distinct disease entities.
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