دورية أكاديمية
Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.
| العنوان: | Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities. |
|---|---|
| المؤلفون: | Chua KP; Genome Institute of Singapore, Singapore, Singapore., Teng YHF; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore.; Cancer Therapeutics Research Laboratory, National Cancer Center Singapore, Singapore, Singapore., Tan AC; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore.; Duke-NUS Medical School Singapore, Singapore., Takano A; Division of Pathology, Singapore General Hospital, Singapore, Singapore., Alvarez JJS; Genome Institute of Singapore, Singapore, Singapore., Nahar R; Genome Institute of Singapore, Singapore, Singapore., Rohatgi N; Genome Institute of Singapore, Singapore, Singapore., Lai GGY; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Aung ZW; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Yeong JPS; Division of Pathology, Singapore General Hospital, Singapore, Singapore., Lim KH; Division of Pathology, Singapore General Hospital, Singapore, Singapore., Naeini MM; Genome Institute of Singapore, Singapore, Singapore., Kassam I; Genome Institute of Singapore, Singapore, Singapore., Jain A; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Tan WL; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Gogna A; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore, Singapore., Too CW; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore, Singapore., Kanesvaran R; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Ng QS; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Ang MK; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Rajasekaran T; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Anantham D; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore., Phua GC; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore., Tan BS; Department of Vascular and Interventional Radiology, Singapore General Hospital, Singapore, Singapore., Lee YY; Genome Institute of Singapore, Singapore, Singapore., Wang L; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Teo ASM; Genome Institute of Singapore, Singapore, Singapore., Khng AJ; Genome Institute of Singapore, Singapore, Singapore., Lim MJ; Genome Institute of Singapore, Singapore, Singapore., Suteja L; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Toh CK; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Lim WT; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore.; Duke-NUS Medical School Singapore, Singapore.; IMCB NCC MPI Singapore Oncogenome Laboratory, Institute of Molecular and Cell Biology, Singapore, Singapore., Iyer NG; Cancer Therapeutics Research Laboratory, National Cancer Center Singapore, Singapore, Singapore.; Duke-NUS Medical School Singapore, Singapore.; Division of Surgical Oncology, National Cancer Center Singapore, Singapore, Singapore., Tam WL; Genome Institute of Singapore, Singapore, Singapore.; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Tan EH; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore., Zhai W; Genome Institute of Singapore, Singapore, Singapore.; Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China., Hillmer AM; Genome Institute of Singapore, Singapore, Singapore.; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany., Skanderup AJ; Genome Institute of Singapore, Singapore, Singapore. daniel.tan.s.w@singhealth.com.sg skanderupamj@gis.a-star.edu.sg., Tan DSW; Genome Institute of Singapore, Singapore, Singapore. daniel.tan.s.w@singhealth.com.sg skanderupamj@gis.a-star.edu.sg.; Division of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore.; Cancer Therapeutics Research Laboratory, National Cancer Center Singapore, Singapore, Singapore.; Duke-NUS Medical School Singapore, Singapore. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Nov 01; Vol. 27 (21), pp. 5939-5950. Date of Electronic Publication: 2021 Jul 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| مواضيع طبية MeSH: | Mutation*, Carcinoma, Non-Small-Cell Lung/*drug therapy , Carcinoma, Non-Small-Cell Lung/*genetics , Lung Neoplasms/*drug therapy , Lung Neoplasms/*genetics, ErbB Receptors/genetics ; Humans ; Protein-Tyrosine Kinases/genetics |
| مستخلص: | Purpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR -mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFR T790M -negative resistance. Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR -mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M + ) and -negative (T790M - ) disease. Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M - tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M - tumors. Almost half of resistant tumors were further classified as immune hot , with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M - and T790M + disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. Conclusions: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR -mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential. (©2021 The Authors; Published by the American Association for Cancer Research.) |
| References: | J Med Econ. 2020 Nov;23(11):1330-1339. (PMID: 32886557) Sci Immunol. 2020 Jan 31;5(43):. (PMID: 32005679) N Engl J Med. 2020 Sep 3;383(10):944-957. (PMID: 32877583) N Engl J Med. 2020 Jan 2;382(1):41-50. (PMID: 31751012) N Engl J Med. 2017 Feb 16;376(7):629-640. (PMID: 27959700) Lung Cancer. 2019 Jan;127:37-43. (PMID: 30642549) Cell Death Differ. 2010 Jan;17(1):93-102. (PMID: 19498444) J Thorac Oncol. 2017 Feb;12(2):403-407. (PMID: 27765535) Nat Commun. 2013;4:2612. (PMID: 24113773) Nature. 2019 Mar;567(7749):479-485. (PMID: 30894752) N Engl J Med. 2009 Sep 3;361(10):947-57. (PMID: 19692680) Ann Oncol. 2018 Jan 1;29(suppl_1):i10-i19. (PMID: 29462254) Cell Syst. 2018 Mar 28;6(3):271-281.e7. (PMID: 29596782) Nat Genet. 2020 Feb;52(2):177-186. (PMID: 32015526) N Engl J Med. 2016 Sep 22;375(12):1109-12. (PMID: 27653561) J Thorac Oncol. 2018 Nov;13(11):1668-1675. (PMID: 30056164) Expert Rev Anticancer Ther. 2019 Jun;19(6):431-435. (PMID: 30950666) Front Immunol. 2020 Jul 14;11:1479. (PMID: 32760402) N Engl J Med. 2017 Jun 1;376(22):2109-2121. (PMID: 28445112) Eur J Health Econ. 2020 Feb;21(1):153-164. (PMID: 31541309) Lancet Oncol. 2016 May;17(5):577-89. (PMID: 27083334) Future Oncol. 2019 Sep;15(25):2905-2914. (PMID: 31370698) Lancet Oncol. 2017 Nov;18(11):1454-1466. (PMID: 28958502) Sci Transl Med. 2015 Apr 15;7(283):283ra54. (PMID: 25877892) Cancer Res. 2013 Dec 15;73(24):7301-12. (PMID: 24170126) Nature. 2014 Jul 31;511(7511):543-50. (PMID: 25079552) Clin Cancer Res. 2013 Apr 15;19(8):2240-7. (PMID: 23470965) J Thorac Oncol. 2016 Nov;11(11):2022-2026. (PMID: 27553514) N Engl J Med. 2018 Jan 11;378(2):113-125. (PMID: 29151359) Nat Rev Cancer. 2019 Jan;19(1):9-31. (PMID: 30532012) Clin Cancer Res. 2019 Feb 15;25(4):1248-1260. (PMID: 30352902) Clin Cancer Res. 2018 Jul 1;24(13):3108-3118. (PMID: 29530932) Nat Med. 2018 Oct;24(10):1550-1558. (PMID: 30127393) Cancer Res. 2019 Sep 1;79(17):4439-4452. (PMID: 31273063) Cell. 2020 Sep 3;182(5):1232-1251.e22. (PMID: 32822576) Cancers (Basel). 2019 Sep 24;11(10):. (PMID: 31554160) J Clin Oncol. 2020 Jan 10;38(2):124-136. (PMID: 31411950) Lancet Oncol. 2019 Dec;20(12):1655-1669. (PMID: 31591063) Cancer Res. 2021 Apr 1;81(7):1802-1812. (PMID: 33547160) Lung Cancer. 2019 Aug;134:42-45. (PMID: 31319993) Lung Cancer. 2018 Nov;125:1-7. (PMID: 30429004) Pathology. 2018 Apr;50(3):333-341. (PMID: 29429740) Front Immunol. 2018 May 30;9:1209. (PMID: 29899747) Science. 2018 Oct 12;362(6411):. (PMID: 30309915) JAMA Oncol. 2020 Jul 1;6(7):1048-1054. (PMID: 32463456) PLoS One. 2012;7(5):e36530. (PMID: 22590557) Lung Cancer. 2016 Nov;101:1-8. (PMID: 27794396) Bioinformatics. 2017 Oct 01;33(19):3131-3133. (PMID: 28605519) Sci Transl Med. 2011 Mar 23;3(75):75ra26. (PMID: 21430269) Stat Med. 2007 Aug 30;26(19):3661-75. (PMID: 17315184) PLoS One. 2012;7(7):e41017. (PMID: 22815900) JAMA Oncol. 2018 Aug 1;4(8):1080-1084. (PMID: 29852038) Nat Commun. 2018 Jan 15;9(1):216. (PMID: 29335443) JAMA Oncol. 2018 Feb 01;4(2):210-216. (PMID: 29270615) Cancer Discov. 2015 Aug;5(8):850-9. (PMID: 25971938) Future Oncol. 2020 Aug;16(22):1585-1595. (PMID: 32757853) Nature. 2012 Sep 27;489(7417):519-25. (PMID: 22960745) J Clin Oncol. 2020 Jan 10;38(2):115-123. (PMID: 31682542) Lancet Oncol. 2012 Mar;13(3):239-46. (PMID: 22285168) J Thorac Oncol. 2019 Feb;14(2):193-202. (PMID: 30391576) JTO Clin Res Rep. 2022 Sep 21;3(12):100416. (PMID: 36426287) JAMA Oncol. 2018 Nov 1;4(11):1527-1534. (PMID: 30073261) Clin Cancer Res. 2019 Feb 1;25(3):1063-1069. (PMID: 30045933) |
| المشرفين على المادة: | EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ErbB Receptors) EC 2.7.10.1 (Protein-Tyrosine Kinases) |
| تواريخ الأحداث: | Date Created: 20210715 Date Completed: 20220331 Latest Revision: 20240906 |
| رمز التحديث: | 20240906 |
| مُعرف محوري في PubMed: | PMC9401458 |
| DOI: | 10.1158/1078-0432.CCR-20-4607 |
| PMID: | 34261696 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
|---|---|
| DOI: | 10.1158/1078-0432.CCR-20-4607 |