دورية أكاديمية
Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities.
| العنوان: | Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. |
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| المؤلفون: | Gay CM; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Stewart CA; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Park EM; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Diao L; Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Groves SM; Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA., Heeke S; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Nabet BY; Department of Oncology Biomarker Development, Genentech Inc., South San Francisco CA, USA., Fujimoto J; Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Solis LM; Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lu W; Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Xi Y; Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Cardnell RJ; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang Q; Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Fabbri G; AstraZeneca, Waltham, MA, USA., Cargill KR; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Vokes NI; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ramkumar K; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang B; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Della Corte CM; Department of Precision Medicine, Oncology Division, University of Campania 'Luigi Vanvitelli', Naples, Italy., Robson P; The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA., Swisher SG; Department of Thoracic and Cardiovascular Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Roth JA; Department of Thoracic and Cardiovascular Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Glisson BS; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Shames DS; Department of Oncology Biomarker Development, Genentech Inc., South San Francisco CA, USA., Wistuba II; Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang J; Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Quaranta V; Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN, USA., Minna J; Department of Internal Medicine and Simmons Cancer Center, the University of Texas Southwestern Medical Center, Dallas, TX, USA., Heymach JV; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA., Byers LA; Department of Thoracic/Head & Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: lbyers@mdanderson.org. |
| المصدر: | Cancer cell [Cancer Cell] 2021 Mar 08; Vol. 39 (3), pp. 346-360.e7. Date of Electronic Publication: 2021 Jan 21. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Immunity/*immunology , Lung Neoplasms/*immunology , Small Cell Lung Carcinoma/*immunology , Transcription Factors/*immunology, Animals ; Cell Line, Tumor ; Cisplatin/pharmacology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/immunology ; Humans ; Immunity/drug effects ; Lung Neoplasms/drug therapy ; Mice, Nude ; Prognosis ; Small Cell Lung Carcinoma/drug therapy ; Mice |
| مستخلص: | Despite molecular and clinical heterogeneity, small cell lung cancer (SCLC) is treated as a single entity with predictably poor results. Using tumor expression data and non-negative matrix factorization, we identify four SCLC subtypes defined largely by differential expression of transcription factors ASCL1, NEUROD1, and POU2F3 or low expression of all three transcription factor signatures accompanied by an Inflamed gene signature (SCLC-A, N, P, and I, respectively). SCLC-I experiences the greatest benefit from the addition of immunotherapy to chemotherapy, while the other subtypes each have distinct vulnerabilities, including to inhibitors of PARP, Aurora kinases, or BCL-2. Cisplatin treatment of SCLC-A patient-derived xenografts induces intratumoral shifts toward SCLC-I, supporting subtype switching as a mechanism of acquired platinum resistance. We propose that matching baseline tumor subtype to therapy, as well as manipulating subtype switching on therapy, may enhance depth and duration of response for SCLC patients. Competing Interests: Declaration of interests C.M.G. reports research funding from AstraZeneca. S.H. reports consulting/honoraria from Qiagen, Boehringer Ingelheim and travel funding from Roche. B.Y.Z. and D.S.S. are employees of Genentech, Inc. G.F. is an employee of AstraZeneca and has stock ownership in AstraZeneca. B.G. reports research funding from ISA Pharm, Cue Bio, Pfizer, and Medimmune. I.I.W. reports consulting/advisory roles for Medscape, MSD, Genentech/Roche, PlatformQ Health, Pfizer, Bayer, Bristol-Myers Squibb, AstraZeneca/Medimmune, HTG Molecular, Asuragen, Merck, GlaxoSmithKline, Guardant Health, Oncocyte, and MSD, research support from Genentech, Oncoplex, HTG Molecular, DepArray, Merck, Bristol-Myers Squibb, Medimmune, Adapative, Adaptimmune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis and Akoya. J.V.H. serves on advisory committees for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Guardant Health, Kairos Venture Investments, BrightPath Biotherapeutics, Hengrui Therapeutics, Eli Lilly, Spectrum, EMD Serono, Roche, and Foundation One Medicine and has research support from AstraZeneca, Spectrum, and Checkmate Pharmaceuticals, as well as royalties/licensing fees from Spectrum and Bio-Tree Systems. L.A.B. serves on advisory committees for AstraZeneca, AbbVie, GenMab, BergenBio, Pharma Mar SA, Sierra Oncology, Merck, Bristol-Myers Squibb, Genentech, and Pfizer and has research support from AbbVie, AstraZeneca, GenMab, Sierra Oncology, Tolero Pharmaceuticals. C.M.G., L.A.B., and J.V.H. have pending patent applications for SCLC subtyping U.S. 62/895,322. Otherwise, there are no pertinent financial or non-financial conflicts of interest to report. (Copyright © 2020 Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cancer Cell. 2021 Mar 8;39(3):297-299. (PMID: 33577787) |
| References: | Nat Biotechnol. 2019 Jul;37(7):773-782. (PMID: 31061481) Clin Cancer Res. 2018 Jan 15;24(2):360-369. (PMID: 29118061) Lancet Oncol. 2017 Oct;18(10):e563. (PMID: 28844817) Nat Rev Cancer. 2019 May;19(5):289-297. (PMID: 30926931) J Thorac Oncol. 2020 Apr;15(4):618-627. (PMID: 31870883) Cancer Discov. 2019 Oct;9(10):1372-1387. (PMID: 31416802) Oncotarget. 2017 Apr 25;8(17):28575-28587. (PMID: 28212573) Nature. 2015 Aug 6;524(7563):47-53. (PMID: 26168399) N Engl J Med. 2018 Dec 6;379(23):2220-2229. (PMID: 30280641) Oncotarget. 2017 Sep 1;8(43):73419-73432. (PMID: 29088717) Lancet Oncol. 2016 Jul;17(7):883-895. (PMID: 27269741) Cancer Discov. 2012 Sep;2(9):798-811. (PMID: 22961666) Nature. 2018 Aug;560(7719):494-498. (PMID: 30089906) J Clin Invest. 2017 Aug 1;127(8):2930-2940. (PMID: 28650338) Nat Med. 2018 Aug;24(8):1143-1150. (PMID: 30038220) J Clin Oncol. 2019 Feb 1;37(4):318-327. (PMID: 30557521) Clin Cancer Res. 2019 Jan 1;25(1):346-357. (PMID: 30257981) Cell Rep. 2016 Aug 2;16(5):1259-1272. (PMID: 27452466) Cancer Cell. 2017 Feb 13;31(2):270-285. (PMID: 28089889) Am Soc Clin Oncol Educ Book. 2018 May 23;38:682-695. (PMID: 30231367) J Clin Oncol. 2017 Oct 10;35(29):3338-3346. (PMID: 28817371) Clin Cancer Res. 2012 Jun 1;18(11):3163-9. (PMID: 22496272) J Clin Oncol. 2018 Aug 10;36(23):2386-2394. (PMID: 29906251) PLoS One. 2014 Jun 24;9(6):e100249. (PMID: 24959847) J Thorac Oncol. 2020 May;15(5):777-791. (PMID: 32068166) Clin Cancer Res. 2017 Jan 15;23(2):523-535. (PMID: 27440269) Oncotarget. 2016 Nov 22;7(47):76534-76550. (PMID: 27708213) Cell. 2015 Jan 15;160(1-2):48-61. (PMID: 25594174) Clin Cancer Res. 2016 Feb 1;22(3):609-20. (PMID: 26420858) Nat Methods. 2015 May;12(5):453-7. (PMID: 25822800) Mol Cancer Ther. 2018 Jan;17(1):196-203. (PMID: 29079710) Nat Cancer. 2020 Apr;1(4):437-451. (PMID: 35121965) J Thorac Oncol. 2020 Feb;15(2):274-287. (PMID: 31655296) Transl Lung Cancer Res. 2018 Feb;7(1):32-49. (PMID: 29535911) Cancer Res. 1985 Jun;45(6):2924-30. (PMID: 2985258) J Natl Cancer Inst. 2016 Oct 5;109(1):. (PMID: 27707838) Cell Rep. 2019 Jun 11;27(11):3345-3358.e4. (PMID: 31189116) Lung Cancer. 2011 Dec;74(3):481-5. (PMID: 21620511) Nat Cancer. 2020 Apr;1:423-436. (PMID: 33521652) Cancer. 2015 Mar 1;121(5):664-72. (PMID: 25336398) Genes Dev. 2018 Jul 1;32(13-14):915-928. (PMID: 29945888) Cancer Discov. 2019 May;9(5):646-661. (PMID: 30777870) Nat Med. 2014 Aug;20(8):897-903. (PMID: 24880617) J Thorac Oncol. 2020 Dec;15(12):1823-1835. (PMID: 33011388) Nat Biotechnol. 2018 Jun;36(5):411-420. (PMID: 29608179) Mol Cancer Ther. 2019 Nov;18(11):1926-1936. (PMID: 31649014) Nature. 2017 May 18;545(7654):360-364. (PMID: 28489825) Lancet. 2019 Nov 23;394(10212):1929-1939. (PMID: 31590988) Expert Opin Biol Ther. 2019 May;19(5):423-432. (PMID: 30855195) Cancer Cell. 2020 Jul 13;38(1):60-78.e12. (PMID: 32473656) Cancer Discov. 2015 Aug;5(8):860-77. (PMID: 26069186) Clin Cancer Res. 2019 Aug 15;25(16):5107-5121. (PMID: 31164374) Clin Cancer Res. 2013 Jan 1;19(1):279-90. (PMID: 23091115) J Natl Cancer Inst. 2016 May 31;108(10):. (PMID: 27247353) Cancer Discov. 2019 Jun;9(6):722-737. (PMID: 31015319) Genome Biol. 2019 Mar 19;20(1):59. (PMID: 30890159) Sci Rep. 2013;3:1911. (PMID: 23714854) Cancer Immunol Immunother. 2017 Nov;66(11):1425-1436. (PMID: 28660319) Cancer Res. 1985 Jun;45(6):2913-23. (PMID: 2985257) Cancer Cell. 2018 May 14;33(5):853-861.e4. (PMID: 29731394) J Med Chem. 2019 Mar 14;62(5):2708-2719. (PMID: 30735385) Cancer Discov. 2019 Jan;9(1):34-45. (PMID: 30297358) |
| معلومات مُعتمدة: | P30 CA016672 United States CA NCI NIH HHS; U24 CA213274 United States CA NCI NIH HHS; R50 CA243698 United States CA NCI NIH HHS; R01 CA207295 United States CA NCI NIH HHS; P50 CA070907 United States CA NCI NIH HHS; T32 CA009666 United States CA NCI NIH HHS; U01 CA215845 United States CA NCI NIH HHS; U01 CA213273 United States CA NCI NIH HHS; P30 CA034196 United States CA NCI NIH HHS; U01 CA213338 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: ASCL1; EMT; NEUROD1; POU2F3; SCLC; intratumoral heterogeneity; neuroendocrine |
| المشرفين على المادة: | 0 (Transcription Factors) Q20Q21Q62J (Cisplatin) |
| تواريخ الأحداث: | Date Created: 20210122 Date Completed: 20210928 Latest Revision: 20240402 |
| رمز التحديث: | 20240402 |
| مُعرف محوري في PubMed: | PMC8143037 |
| DOI: | 10.1016/j.ccell.2020.12.014 |
| PMID: | 33482121 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
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| DOI: | 10.1016/j.ccell.2020.12.014 |