小细胞肺癌个体化治疗进展

张爽; 柳菁菁; 程颖

doi:10.3969/j.issn.1000-8179.2017.12.171

小细胞肺癌个体化治疗进展

doi: 10.3969/j.issn.1000-8179.2017.12.171

吉林省肿瘤医院胸部肿瘤内科（长春市130012）

基金项目:

本文课题受吉林省卫生计生科研计划项目基金（编号： 2014Z014

详细信息

作者简介:
张爽专业方向为肺癌的临床诊治及转化研究。E-mail：zhangshuangphy@126.com

程颖教授，主任医师，博士研究生导师，享受国务院特殊津贴，卫生部有突出贡献中青年专家。现任吉林省肿瘤医院院长、吉林省肿瘤研究所所长、吉林省抗癌协会理事长。担任中国临床肿瘤学会（CSCO）副理事长、CSCO小细胞肺癌专家委员会主任委员、中国抗癌协会常务理事、中国抗癌协会肺癌专业委员会副主任委员、中国抗癌协会肿瘤临床化疗专业委员会副主任委员、中华医学会肿瘤学分会委员、中国医师协会肺癌专业委员会副主任委员、吉林省医师协会肿瘤医师分会主任委员、吉林省抗癌协会肿瘤精准医学及药物治疗专业委员会主任委员，吉林省医学会肿瘤专业委员会主任委员等。担任《中华肿瘤学杂志》等多个杂志编委。承担国家十二五、十一五重大科技攻关、863、国家自然科学基金在内多个科研课题。撰写学术论著27部。发表论文140余篇，SCI收录29篇.

通讯作者:
程颖 jl.cheng@163.com

计量
- 文章访问数: 89
- HTML全文浏览量: 36
- PDF下载量: 11
- 被引次数: 0
出版历程
- 收稿日期: 2017-02-15
- 修回日期: 2017-04-25
- 刊出日期: 2017-06-30

Advances in personalized treatment of small cell lung cancer

Department of Thoracic Medical Oncology, Jilin Provincial Cancer Hospital, Changchun 130012, China

摘要

摘要: 小细胞肺癌（small cell lung cancer，SCLC）具有进展迅速、早期转移、预后差的特点。SCLC的治疗一直是研究者关注的焦点。精准医学和个体化医疗的发展打破了SCLC治疗领域多年的沉寂，使SCLC的治疗模式发生改变。生物信息学的进步加速了对SCLC分子机制的理解，发现SCLC个体化治疗的一些潜在靶点，在临床研究中针对这些靶点的药物进行不断的探索，描绘着SCLC个体化医疗的美好前景。
- 小细胞肺癌 /
- 一线治疗 /
- 二线治疗 /
- 分子靶向治疗 /
- 免疫检查点抑制剂
Abstract: Small cell lung cancer (SCLC) is a lethal malignancy characterized by rapid growth, early metastatic spread, and unfavorable survival outcomes. Optimizing treatment for patients with SCLC has been the focus for investigators. The emergence of precision medicine and personalized treatment brought significant breakthroughs into SCLC treatment and changed the therapeutic model. The development of molecular bioinformatics increased our understanding of complex molecular mechanisms of SCLC, and novel targets for personalized treatment have been developed. Clinical trials testing these targets are ongoing, which show the potential of personalized treatment for SCLC.
- small cell lung cancer /
- first-line therapy /
- second-line therapy /
- molecular-target therapy /
- immune checkpoint inhibitors

HTML全文

参考文献(38)

[1]	Schreiber D, Rineer J, Weedon J, et al.Survival outcomes withtheuse of surgery in limited-stage small cell lung cancer: should itsrole bere-evaluated[J]? Cancer.2010, 116(5):1350-1357. doi: 10.1002/cncr.v116:5
[2]	Varlotto JM, Recht A, Flickinger JC, et al.Lobectomy leads to optimal survival in early-stage small cell lung cancer: a retrospective analysis[J].J Thorac Cardiovasc Surg, 2011, 142(3):538-546. doi: 10.1016/j.jtcvs.2010.11.062
[3]	Tsuchiya R, Suzuki K, Ichinose Y, et al.Phase Ⅱ trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage Ⅰ-Ⅲa small cell lung cancer: the Japan Clinical OncologyLung Cancer Study Group Trial(JCOG9101)[J].J Thorac CardiovascSurg, 2005, 129(5):977-983. doi: 10.1016/j.jtcvs.2004.05.030
[4]	Wong AT, Rineer J, Schwartz D, et al.Assessing the impact of postoperative radiation therapy for completely resected limited-stagesmall cell lung cancer using the national cancer database.[J].J Thorac Oncol, 2016, 11(2):242-248. doi: 10.1016/j.jtho.2015.10.011
[5]	Faivre-Finn C, Snee M, Ashcroft L, et al.CONVERT: an international randomised trial of concurrent chemo-radiotherapy(cCTRT)comparing twice-daily(BD)and once-daily(OD)radiotherapy schedulesin patients with limited stage small cell lung cancer(LS-SCLC)and goodperformance status(PS)[J].J Clin Oncol, 2016, 34(15 Suppl):8504. http://abstracts.ncri.org.uk/abstract/convert-an-international-randomised-trial-of-concurrent-chemo-radiotherapy-comparing-twice-daily-and-once-daily-radiotherapy-schedules-in-patients-with-limited-stage-small-cell-lung-cancer/
[6]	Slotman BJ, van Tinteren H, Praag JO, et al.Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial[J].Lancet, 2015, 385(9962):36-42. doi: 10.1016/S0140-6736(14)61085-0
[7]	Meert AP, Paesmans M, Berghmans T, et al.Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis[J].BMC Cancer, 2001, 1:5. doi: 10.1186/1471-2407-1-5
[8]	Patel S, Macdonald OK, Suntharalingam M.Evaluation of the useofprophylactic cranial irradiation in small cell lung cancer [J].Cancer.2009, 115(4):842-850. doi: 10.1002/cncr.v115:4
[9]	Péchoux CL, Sun A, Slotman BJ, et al.Prophylactic cranial irradiationfor patients with lung cancer[J].Lancet Oncol, 2016, 17(7):e277-293. doi: 10.1016/S1470-2045(16)30065-1
[10]	Kundapur V, Ellchuk T, Ahmed S, et al.Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation: a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation[J].Int J RadiatOncol Biol Phys, 2015, 91(4):781-786. doi: 10.1016/j.ijrobp.2014.12.026
[11]	Takahashi T, Yamanaka T, Seto T, et al.Prophylactic cranial irradiation versus observation in patients with extensive-disease smallcell lung cancer: a multicentre, randomised, open-label, phase 3 trial[J].Lancet Oncol, 2017, 18(5):663-671. doi: 10.1016/S1470-2045(17)30230-9
[12]	O'Brien ME, Ciuleanu TE, Tsekov H, et al.Phase Ⅲ trial comparingsupportive care alone with supportive care with oral topotecan inpatients with relapsed small-cell lung cancer[J].J Clin Oncol, 2006, 24(34):5441-5447. doi: 10.1200/JCO.2006.06.5821
[13]	Goto K, Ohe Y, Shibata T, et al.Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as secondline treatment for patients with sensitive relapsed small-cell lungcancer(JCOG0605): a multicentre, open-label, randomised phase 3trial[J].Lancet Oncol, 2016, 17(8):1147-1157. doi: 10.1016/S1470-2045(16)30104-8
[14]	Giet R, Prigent C.Aurora/Ipl1p-related kinases, a new oncogenic familyof mitotic serine-threonine kinases [J].J Cell Sci, 1999, 112(21):3591-3601. https://www.researchgate.net/profile/Regis_Giet/publication/12776048_AuroraIpl1p-related_kinases_a_new_oncogenic_family_of_mitotic_serine-threonine_kinases/links/00463522582c1330e6000000.pdf?origin=publication_detail
[15]	Bavetsias V, Linardopoulos S, Aurora Kinase Inhibitors: Current Status and Outlook[J].Front Oncol, 2015, 5:278. https://pdfs.semanticscholar.org/6cf2/d746a01d5214bc184fc1169315fba15fb121.pdf
[16]	Sos ML, Dietlein F, Peifer M, et al.A framework for identification ofactionable cancer genome dependencies in small cell lung cancer[J].Proc Natl Acad Sci U S A, 2012, 109(42):17034-17039. doi: 10.1073/pnas.1207310109
[17]	Rudin CM, Durinck S, Stawiski EW, et al.Comprehensive genomicanalysis identifies SOX2 as a frequently amplified gene in small-celllung cancer[J].Nat Genet, 2012, 44(10):1111-1116. doi: 10.1038/ng.2405
[18]	Peifer M, Fernández-Cuesta L, Sos ML, et al.Integrative genomeanalyses identify key somatic driver mutations of small-cell lungcancer [J].Nat Genet, 2012, 44(10):1104-1110. doi: 10.1038/ng.2396
[19]	George J, Lim JS, Jang SJ, et al.Comprehensive genomic profiles ofsmall cell lung cancer[J].Nature, 2015, 524(7563):47-53. doi: 10.1038/nature14664
[20]	Jahchan NS, Lim JS, Bola B, et al.Identification and targeting of longterm tumor-propagating cells in small cell lung cancer[J].Cell Rep, 2016, 16(3):644-656. doi: 10.1016/j.celrep.2016.06.021
[21]	Mollaoglu G, Guthrie MR, Böhm S, et al.MYC drives progression ofsmall cell lung cancer to a variant neuroendocrine subtype withvulnerability to aurora kinase inhibition[J].Cancer Cell, 2017, 31(2):270-285. doi: 10.1016/j.ccell.2016.12.005
[22]	Melichar B, Adenis A, Lockhart AC, et al.Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breastcancer, small-cell lung cancer, non-small-cell lung cancer, head andneck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study[J].Lancet Oncol, 2015, 16(4):395-405. doi: 10.1016/S1470-2045(15)70051-3
[23]	Owonikoko TK, Nackaerts K, Csoszi T, et al.Randomized phase 2 studyof investigational aurora A kinase(AAK)inhibitor alisertib(MLN8237)+paclitaxel(P)vs placebo+P as second line therapy for small-cell lungcancer(SCLC)[J].Ann Oncol, 2016, 27(Suppl 6):14230.
[24]	Ali S, Kolla B, Bailey M, et al.Small cell lung carcinoma harbors targetable alterations including MYCL1 fusions responding to aurorakinase inhibitor[J].Ann Oncol, 2016, 27(Suppl 6):14240. http://oncologypro.esmo.org/Meeting-Resources/ESMO-2016/Small-cell-lung-carcinoma-harbors-targetable-alterations-including-MYCL1-fusions-responding-to-aurora-kinase-inhibitor
[25]	Perez HL, Cardarelli PM, Deshpande S, et al.Antibody-drug conjugates:current status and future directions[J].Drug Discov Today, 2014, 19(7):869-81. doi: 10.1016/j.drudis.2013.11.004
[26]	Saunders LR, Bankovich AJ, Anderson WC, et al.A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo[J].Sci Transl Med, 2015, 7(302):302. http://stm.sciencemag.org/content/scitransmed/7/302/302ra136.full.pdf?ijkey%253DzZet68mMheyYI%2526keytype%253Dref%2526siteid%253Dscitransmed=
[27]	Chapman G, Sparrow DB, Kremmer E, et al.Notch inhibition by theligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis[J].Hum Mol Genet.2011, 20(5):905-916. doi: 10.1093/hmg/ddq529
[28]	Rudin CM, Pietanza MC, Bauer TM, et al.Safety and efficacy of single-agent rovalpituzumab tesirine(SC16LD6.5), a delta-like protein3(DLL3)-targeted antibody-drug conjugate(ADC)in recurrent or refractory small cell lung cancer(SCLC)[J].J Clin Oncol, 2016, 34.
[29]	Bauer TM, Spigel D, Ready N, et al.ORAL02.01: safety and efficacyof single-agent rovalpituzumab tesirine, a DLL3-targeted ADC, in recurrent or refractory SCLC: topic: medical oncology[J].J Thorac Oncol, 2016, 11(11S):S252-S253. http://meetinglibrary.asco.org/record/125334/video
[30]	Reck M, Luft A, Szczesna A, et al.Phase Ⅲ randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer[J].J ClinOncol, 2016, pii: JCO676601[Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27458307/
[31]	Gao J, Shi LZ, Zhao H, et al.Loss of IFN-γ pathway genes in tumorcells as a mechanism of resistance to anti-CTLA-4 therapy[J].Cell, 2016, 167(2):397-404. doi: 10.1016/j.cell.2016.08.069
[32]	Arriola E, Wheater M, Galea I, et al.Outcome and biomarker analysis from a multicenter phase 2 study of ipilimumab in combinationwith carboplatin and etoposide as first-line therapy for extensivestage SCLC[J].J Thorac Oncol, 2016, 11(9):1511-1521. doi: 10.1016/j.jtho.2016.05.028
[33]	Antonia SJ, López-Martin JA, Bendell J, et al.Nivolumab alone andnivolumab plus ipilimumab in recurrent small-cell lung cancer(CheckMate 032): a multicentre, open-label, phase 1/2 trial[J].Lancet Oncol, 2016, 17(7):883-895. doi: 10.1016/S1470-2045(16)30098-5
[34]	Meder L, König K, Ozretić L, et al.NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine andsmall cell lung carcinomas[J].Int J Cancer, 2016, 138(4):927-938. doi: 10.1002/ijc.29835
[35]	Borromeo MD, Savage TK, Kollipara RK, et al.ASCL1 and NEUROD1reveal heterogeneity in pulmonary neuroendocrine tumors andregulate distinct genetic programs[J].Cell Rep, 2016, 16(5):1259-1272. doi: 10.1016/j.celrep.2016.06.081
[36]	Dooley AL, Winslow MM, Chiang DY, et al.Nuclear factor I/B is anoncogene in small cell lung cancer [J].Genes Dev, 2011, 25(14):1470-1475. doi: 10.1101/gad.2046711
[37]	Denny SK, Yang D, Chuang CH, et al.Nfib promotes metastasis througha widespread increase in chromatin accessibility[J].Cell, 2016, 166(2):328-342. doi: 10.1016/j.cell.2016.05.052
[38]	Carter L, Rothwell DG, Mesquita B, et al.Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lungcancer[J].Nat Med, 2017, 23(1):114-119. http://www.christie.nhs.uk/media/4755/molecular-analysis-of-circulating-tumor-cells-identifies-distinct-copy-number-profiles.pdf