Journal ArticleDOI
Targeting the cell signaling pathway Keap1-Nrf2 as a therapeutic strategy for adenocarcinomas of the lung.
TLDR
It is suggested that the rational combination of Nrf2 suppression with chemical agents which cause enhanced oxidative imbalance or abnormal metabolism would be promising in the treatment of lung adenocarcinoma.Abstract:
Introduction: Kelch-like ECH associated protein 1/Nuclear factor erythroid 2-like factor 2 (Keap1-Nrf2) signaling plays a pivotal role in response to oxidative stress in lung cancer. Mutations in KEAP1/NFE2L2 genes always cause persistent Nrf2 activation in lung cancer cells that confer therapeutic resistance and aggressive tumorigenic activity, dictating either poor prognosis or short duration of response to chemotherapy in clinical observations.Areas covered: We provide a review of the mechanisms underlying the regulation of Keap1-Nrf2 at different stages, including genetic mutations, epigenetic modifications, translational/post-translational alterations, and protein–protein interactions. Based on the current knowledge, we discuss the possibilities of intervening Keap1-Nrf2 in lung adenocarcinoma as a therapeutic target.Expert opinion: It is prevalently conceived that Keap1-Nrf2 signaling plays different roles at diverse stages of cancer. Although various Nrf2 or Keap1 inhibitors have been repor...read more
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Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance
Eric Santoni-Rugiu,Linea Melchior,E. Urbanska,Jan Nyrop Jakobsen,Karin de Stricker,Morten Grauslund,Jens Benn Sørensen +6 more
TL;DR: The review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.
Journal ArticleDOI
Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2
Sha Huang,Tianyu He,Sijia Yang,Hongxu Sheng,Xiuwen Tang,Feichao Bao,Yiqing Wang,Xu Lin,Wenfeng Yu,Fei Cheng,Wang Lv,Jian Hu +11 more
TL;DR: In this paper, the effects of combination therapy with metformin and cisplatin on cell proliferation and apoptosis, intracellular reactive oxygen species (ROS) levels, and xenograft tumor formation were analyzed in NSCLC cells.
Journal ArticleDOI
Natural compounds targeting cancer stem cells: a promising resource for chemotherapy
Plabon Kumar Das,Tasnim Zahan,Abdur Rakib,Jahan Ara Khanam,Suja Pillai,Farhadul Islam,Farhadul Islam +6 more
TL;DR: This review has described the key signaling pathways activated in CSCs to maintain their survival and highlighted how natural compounds interrupt these signaling pathways to minimize therapy resistance, pathogenesis and cancer recurrence properties of C SCs, thereby providing useful strategies to treat cancer or aid in cancer therapy improvement.
Journal ArticleDOI
Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas
TL;DR: In this paper, the authors reviewed the advances in oxidative stress and Nrf2-mediated oxidative stress response signaling pathways in pituitary tumorigenesis, and the potential of targeting nrf2 signaling pathways as a new therapeutic strategy for PAs.
Journal ArticleDOI
KEAP1/NRF2 (NFE2L2) mutations in NSCLC - Fuel for a superresistant phenotype?
Wolfram C. M. Dempke,Martin Reck +1 more
TL;DR: In this paper, the authors highlight the molecular features, the key components, and possible inhibitors of the KEAP1/NRF2 pathway, its role as prognostic and predictive biomarker, and the resulting clinical implications in NSCLC patients.
References
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Journal ArticleDOI
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TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
Journal ArticleDOI
Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
Eric A. Collisson,Joshua D. Campbell,Angela N. Brooks,Angela N. Brooks,Alice H. Berger,William Lee,Juliann Chmielecki,David G. Beer,Leslie Cope,Chad J. Creighton,Ludmila Danilova,Li Ding,Gad Getz,Gad Getz,Peter S. Hammerman,D. Neil Hayes,Bryan Hernandez,James G. Herman,John V. Heymach,Igor Jurisica,Raju Kucherlapati,David J. Kwiatkowski,Marc Ladanyi,Gordon Robertson,Nikolaus Schultz,Ronglai Shen,Rileen Sinha,Carrie Sougnez,Ming-Sound Tsao,William D. Travis,John N. Weinstein,Dennis A. Wigle,Matthew D. Wilkerson,Andy Chu,Andrew D. Cherniack,Angela Hadjipanayis,Mara Rosenberg,Daniel J. Weisenberger,Peter W. Laird,Amie Radenbaugh,Singer Ma,Joshua M. Stuart,Lauren Averett Byers,Stephen B. Baylin,Ramaswamy Govindan,Matthew Meyerson,Matthew Meyerson,Stacey Gabriel,Kristian Cibulskis,Jaegil Kim,Chip Stewart,Lee Lichtenstein,Eric S. Lander,Eric S. Lander,Michael S. Lawrence,E. Getz,E. Getz,Robert S. Fulton,Lucinda Fulton,Michael D. McLellan,Richard K. 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Broom,Jing Wang,Yiling Lu,Patrick Kwok Shing Ng,Lixia Diao,Wenbin Liu,Christopher I. Amos,Rehan Akbani,Gordon B. Mills,Erin Curley,Joseph Paulauskis,Kevin Lau,Scott Morris,Troy Shelton,David Mallery,Johanna Gardner,Robert Penny,Charles Saller,Katherine Tarvin,William G. Richards,Robert J. Cerfolio,Ayesha S. Bryant,Daniel P. Raymond,Nathan A. Pennell,Carol Farver,Christine Czerwinski,Lori Huelsenbeck-Dill,Mary Iacocca,Nicholas J. Petrelli,Brenda Rabeno,Jennifer Brown,Thomas L. Bauer,Cureline Oleg Dolzhanskiy,Olga Potapova,D L Rotin,Olga Voronina,Elena Nemirovich-Danchenko,Konstantin V. Fedosenko,Anthony A. Gal,Madhusmita Behera,Suresh S. Ramalingam,Gabriel Sica,Douglas B. Flieder,Jeff Boyd,Jo Ellen Weaver,Bernard Kohl,Dang Huy Quoc Thinh,George E. Sandusky,Hartmut Juhl,Edwina Duhig,Peter B. Illei,Edward Gabrielson,James Shin,Beverly Lee,Kristen Rogers,Dante Trusty,Malcolm V. Brock,Christina Williamson,Eric J. Burks,Kimberly M. Rieger-Christ,Antonia H. Holway,Travis Sullivan,Michael K. Asiedu,Farhad Kosari,Natasha Rekhtman,Maureen F. Zakowski,Valerie W. Rusch,Paul Zippile,James Suh,Harvey I. Pass,Chandra Goparaju,Yvonne Owusu-Sarpong,John M. S. Bartlett,Sugy Kodeeswaran,Jeremy Parfitt,Harmanjatinder S. Sekhon,Monique Albert,John Eckman,Jerome Myers,Carl Morrison,Carmelo Gaudioso,Jeffrey A. Borgia,Philip Bonomi,Mark Pool,Michael J. Liptay,Fedor Moiseenko,Irina Zaytseva,Hendrik Dienemann,Michael Meister,Philipp A. Schnabel,Thomas Muley,Martin Peifer,Carmen Gomez-Fernandez,Lynn M. Herbert,Sophie C. Egea,Mei Huang,Leigh B. Thorne,Lori Boice,Ashley H. Salazar,William K. Funkhouser,W. Kimryn Rathmell,Rajiv Dhir,Samuel A. Yousem,Sanja Dacic,Frank Schneider,Jill M. Siegfried,Richard A. Hajek,Mark A. Watson,Sandra McDonald,Bryan F. Meyers,Belinda E. Clarke,Ian A. Yang,Kwun M. Fong,Lindy Hunter,Morgan Windsor,Rayleen V. Bowman,Solange Peters,Igor Letovanec,Khurram Z. Khan,Mark A. Jensen,Eric E. Snyder,Deepak Srinivasan,Ari B. Kahn,Julien Baboud,David Pot,Kenna R. Mills Shaw,Margi Sheth,Tanja Davidsen,John A. Demchok,Liming Yang,Zhining Wang,Roy Tarnuzzer,Jean C. Zenklusen,Bradley A. Ozenberger,Heidi J. Sofia,Richard T. Cheney +318 more
TL;DR: In this paper, the authors report molecular profiling of 230 resected lung adnocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses.
Comprehensive molecular profiling of lung adenocarcinoma
TL;DR: High rates of somatic mutation were seen, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification, and MAPK and PI(3)K pathway activity was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation.
Journal ArticleDOI
Modulation of oxidative stress as an anticancer strategy.
TL;DR: The controversial role of ROS in tumour development and in responses to anticancer therapies is addressed, and the idea that targeting the antioxidant capacity of tumour cells can have a positive therapeutic impact is elaborate.