New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness

被引：100

作者：

Yang, Haitang ^{[1
]}

Liang, Shun-Qing ^{[1
,2
]}

Schmid, Ralph A. ^{[1
]}

Peng, Ren-Wang ^{[1
]}

机构：

[1] Univ Bern, Bern Univ Hosp, Dept Gen Thorac Surg, Dept BioMed Res,Inselspital, Bern, Switzerland

[2] Univ Massachusetts, Sch Med, Worcester, MA USA

来源：

FRONTIERS IN ONCOLOGY | 2019年 / 9卷

关键词：

lung cancer; KRAS; mitogen-activated protein kinases; heterogeneity; targeted therapy; immunotherapy; COOCCURRING GENOMIC ALTERATIONS; SELUMETINIB PLUS DOCETAXEL; PROGRESSION-FREE SURVIVAL; K-RAS; MEK INHIBITION; PHASE-II; C-RAF; MUTATION; ONCOGENE; THERAPY;

D O I：

10.3389/fonc.2019.00953

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In non-small cell lung cancer (NSCLC), the most frequent oncogenic mutation in western countries is KRAS, for which, however, there remains no clinically approved targeted therapies. Recent progress on high biological heterogeneity including diverse KRAS point mutations, varying dependence on mutant KRAS, wide spectrum of other co-occurring genetic alterations, as well as distinct cellular status across the epithelial-to-mesenchymal transition (EMT), has not only deepened our understanding about the pathobiology of KRAS-mutant NSCLC but also brought about unprecedented new hopes for precision treatment of patients. In this review, we provide an update on the most recent advances in KRAS-mutant lung cancer, with a focus on mechanistic insights into tumor heterogeneity, the potential clinic implications and new therapies on horizons tailored for KRAS-mutant lung cancer.

引用

页数：13

共 103 条

[1]

[Anonymous], CORRELATION MUTATI S

[2] Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS-Mutant Non-Small Cell Lung Cancer [J].

Arbour, Kathryn C. ;

Jordan, Emmett ;

Kim, Hyunjae Ryan ;

Dienstag, Jordan ;

Yu, Helena A. ;

Sanchez-Vega, Francisco ;

Lito, Piro ;

Berger, Michael ;

Solit, David B. ;

Hellmann, Matthew ;

Kris, Mark G. ;

Rudin, Charles M. ;

Ni, Ai ;

Arcila, Maria ;

Ladanyi, Marc ;

Riely, Gregory J. .

CLINICAL CANCER RESEARCH, 2018, 24 (02) :334-340

[3] c-Raf, but Not B-Raf, Is Essential for Development of K-Ras Oncogene-Driven Non-Small Cell Lung Carcinoma [J].

Blasco, Rafael B. ;

Francoz, Sarah ;

Santamaria, David ;

Canamero, Marta ;

Dubus, Pierre ;

Charron, Jean ;

Baccarini, Manuela ;

Barbacid, Mariano .

CANCER CELL, 2011, 19 (05) :652-663

[4] A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC) [J].

Blumenschein, G. R., Jr. ;

Smit, E. F. ;

Planchard, D. ;

Kim, D. -W. ;

Cadranel, J. ;

De Pas, T. ;

Dunphy, F. ;

Udud, K. ;

Ahn, M. -J. ;

Hanna, N. H. ;

Kim, J. -H. ;

Mazieres, J. ;

Kim, S. -W. ;

Baas, P. ;

Rappold, E. ;

Redhu, S. ;

Puski, A. ;

Wu, F. S. ;

Jaenne, P. A. .

ANNALS OF ONCOLOGY, 2015, 26 (05) :894-901

[5] Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors [J].

Boshuizen, Julia ;

Koopman, Louise A. ;

Krijgsman, Oscar ;

Shahrabi, Aida ;

Gresnigt-van den Heuvel, Elke ;

Ligtenberg, Maarten A. ;

Vredevoogd, David W. ;

Kemper, Kristel ;

Kuilman, Thomas ;

Song, Ji-Ying ;

Pencheva, Nora ;

Mortensen, Jens Thing ;

Foppen, Marnix Geukes ;

Rozeman, Elisa A. ;

Blank, Christian U. ;

Janmaat, Maarten L. ;

Satijn, David ;

Breij, Esther C. W. ;

Peeper, Daniel S. ;

Parren, Paul W. H. I. .

NATURE MEDICINE, 2018, 24 (02) :203-+

[6] Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer [J].

Bryant, Kirsten L. ;

Stalnecker, Clint A. ;

Zeitouni, Daniel ;

Klomp, Jennifer E. ;

Peng, Sen ;

Tikunov, Andrey P. ;

Gunda, Venugopal ;

Pierobon, Mariaelena ;

Waters, Andrew M. ;

George, Samuel D. ;

Tomar, Garima ;

Papke, Bjorn ;

Hobbs, G. Aaron ;

Yan, Liang ;

Hayes, Tikvah K. ;

Diehl, J. Nathaniel ;

Goode, Gennifer D. ;

Chaika, Nina V. ;

Wang, Yingxue ;

Zhang, Guo-Fang ;

Witkiewicz, Agnieszka K. ;

Knudsen, Erik S. ;

Petricoin, Emanuel F., III ;

Singh, Pankaj K. ;

Macdonald, Jeffrey M. ;

Tran, Nhan L. ;

Lyssiotis, Costas A. ;

Ying, Haoqiang ;

Kimmelman, Alec C. ;

Cox, Adrienne D. ;

Der, Channing J. .

NATURE MEDICINE, 2019, 25 (04) :628-+

[7] Impact of Systematic EGFR and KRAS Mutation Evaluation on Progression-Free Survival and Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Treated by Erlotinib in a French Prospective Cohort (ERMETIC Project-Part 2) [J].

Cadranel, Jacques ;

Mauguen, Audrey ;

Faller, Michele ;

Zalcman, Gerard ;

Buisine, Marie-Pierre ;

Westeel, Virginie ;

Longchampt, Elisabeth ;

Wislez, Marie ;

Coudert, Bruno ;

Daniel, Catherine ;

Chetaille, Bruno ;

Michiels, Stephane ;

Blons, Helene ;

Solassol, Jerome ;

De Fraipont, Florence ;

Foucher, Pascal ;

Urban, Thierry ;

Lacroix, Ludovic ;

Poulot, Virginie ;

Quoix, Elisabeth ;

Antoine, Martine ;

Danton, Guillaume ;

Morin, Franck ;

Chouaid, Christos ;

Pignon, Jean-Pierre .

JOURNAL OF THORACIC ONCOLOGY, 2012, 7 (10) :1490-1502

[8]

Castellano Esther, 2011, Genes Cancer, V2, P261, DOI 10.1177/1947601911408079

[9] MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road [J].

Caunt, Christopher J. ;

Sale, Matthew J. ;

Smith, Paul D. ;

Cook, Simon J. .

NATURE REVIEWS CANCER, 2015, 15 (10) :577-592

[10] PTPN11 is the first identified proto-oncogene that encodes a tyrosine phosphatase [J].

Chan, Rebecca J. ;

Feng, Gen-Sheng .

BLOOD, 2007, 109 (03) :862-867

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