原发性支气管肺癌分子靶向治疗的研究进展
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摘要
原发性支气管肺癌(简称肺癌)是目前发病率及死亡率最高的恶性肿瘤之一。临床上绝大部分患者初诊时已失去外科手术机会,故其治疗很大程度上依赖于内科治疗。与传统含铂类化疗方案相比,分子靶向治疗药物疗效更佳且全身不良反应少,已被广泛应用于临床实践。本文就肺癌分子靶向治疗进展进行阐述与探讨。
Lung cancer,namely primary bronchial lung cancer,is one of the most common malignant tumors with the highest morbidity and mortality.Most of the patients have lost the opportunity of surgery at first visit,and so the treatment depends on systemic medical treatment.Compared with traditional platinum-based chemotherapy regimens,the precision molecular targeted therapy bring patients better cancer-killing effects with less drug toxicity,and thus have been widely used.The recent advances on molecular targeted therapy for lung cancer are interpreted in this article which may provide a reference for clinical.
Lung cancer,namely primary bronchial lung cancer,is one of the most common malignant tumors with the highest morbidity and mortality.Most of the patients have lost the opportunity of surgery at first visit,and so the treatment depends on systemic medical treatment.Compared with traditional platinum-based chemotherapy regimens,the precision molecular targeted therapy bring patients better cancer-killing effects with less drug toxicity,and thus have been widely used.The recent advances on molecular targeted therapy for lung cancer are interpreted in this article which may provide a reference for clinical.
引文
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[5]Fukuoka M,Wu YL,Thongprasert S,et al.Biomarker analyses and final overall survival results from a phaseⅢ,randomized,open-label,first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced nonsmallcell lung cancer in Asia(IPASS)[J].J Clin Oncol,2011,29(21):2866-2874.
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[21]Mok TS,Wu YL,Ahn MJ,et al.Osimertinib or platinumpemetrexed in EGFR T790M-positive lung cancer[J].N Engl J Med,2017,376(7):629-640.
[22]Soria JC,Ohe Y,Vansteenkiste J,et al.Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J].NEngl J Med,2018,378(2):11 3-125.
[23]Ou SI,Horn L,Cruz M,et al.Emergence of FGFR3-TACC3fusions as a potential by-pass resistance mechanism to EGFR tyrosine kinase inhibitors in EGFR mutated NSCLCpatients[J].Lung Cancer,2017,111:61-64.
[24]Oztan A,Fischer S,Schrock AB,et al.Emergence of EGFRG724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib[J].Lung Cancer,2017,111:84-87.
[25]Uchibori K,Inase N,Araki M,et al.Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer[J].Nat Commun,2017,8:14768-14768.
[26]Sharma P,Allison JP.Immune checkpoint targeting in cancer therapy:toward combination strategies with curative potential[J].Cell,2015,161(2):205-214.
[27]Soda M,Choi YL,Enomoto M,et al.Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer[J].Nature,2007,448(7153):561-566.
[28]Chiarle R,Voena C,Ambrogio C,et al.The anaplastic lymphoma kinase in the pathogenesis of cancer[J].Nat Rev Cancer,2008,8(1):11-23.
[29]Rikova K,Guo A,Zeng Q,e t al.Globa l survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer[J].Cell,2007,131(6):11 90-1203.
[30]Shaw AT,Yeap BY,Mino-Kenudson M,et al.Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK[J].J Clin Oncol,2009,27(26):4247-4253.
[31]Blackhall F,Kim DW,Besse B,et al.Patient-reported outcomes and quality of life in PROFILE 1007:a randomized trial of crizotinib compared with chemotherapy in previously treated patients with ALK-positive advanced non-small-cell lung cancer[J].J Thorac Oncol,2014,9(11):1625-1633.
[32]Solomon BJ,Mok T,Kim DW,et al.First-line crizotinib versus chemotherapy in ALK-positive lung cancer[J].N Engl J Med,2014,371(23):2167-2177.
[33]Choi YL,Soda M,Yamashita Y,et al.EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors[J].NEngl J Med,2010,363(18):1734-1739.
[34]Doebele RC,Pilling AB,Aisner DL,et al.Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer[J].Clin Cancer Res,2012,18(5):1472-1482.
[35]Sasaki T,Koivunen J,Ogino A,et al.A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors[J].Cancer Res,2011,71(18):6051-6060.
[36]Shaw AT,Kim TM,Crino L,et al.Ceritinib versus chemotherapy in patients with ALK-rearranged non-smallcell lung cancer previously given chemotherapy and crizotinib(ASCEND-5):a randomised,controlled,open-label,phase 3trial[J].Lancet Oncol,2017,18(7):874-886.
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[38]Crino L,Ahn MJ,De Marinis F,et al.Multicenter phaseⅡstudy of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib:results from ASCEND-2[J].J Clin Oncol,2016,34(24):2866-2873.
[39]Shaw AT,Gandhi L,Gadgeel S,et al.Alectinib in ALKpositive,crizotinib-resistant,non-small-cell lung cancer:a single-group,multicentre,phase 2 trial[J].Lancet Oncol,2016,17(2):234-242.
[40]Ou SH,Ahn JS,De Petris L,et al.Alectinib in crizotinibrefractory ALK-rearranged non-small-cell lung cancer:a phaseⅡglobal study[J].J Clin Oncol,2016,34(7):661-668.
[41]Hida T,Nokihara H,Kondo M,et al.Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer(J-ALEX):an open-label,randomised phase 3 trial[J].Lancet,2017,390(10089):29-39.
[42]Zhang S,Anjum R,Squillace R,et al.The potent ALKinhibitor brigatinib(AP2611 3)overcomes mechanisms of resistance to first-and second-generation ALK inhibitors in preclinical models[J].Clin Cancer Res,2016,22(22):5527-5538.
[43]Kim DW,Tiseo M,Ahn MJ,et al.Brigatinib in Patients with crizotinib-refractory anaplastic lymphoma kinase-positive nonsmallcell lung cancer:a randomized,multicenter phaseⅡtrial[J].J Clin Oncol,2017,35(22):2490-2498.
[44]Gettinger SN,Bazhenova LA,Langer CJ,et al.Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies:a single-arm,open-label,phase1/2 trial[J].Lancet Oncol,2016,17(12):1683-1696.
[45]Camidge DR,Kim HR,Ahn MJ,et al.Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer[J].NEngl J Med,2018,379(21):2027-2039.
[46]Bo y l e TA,Ma s a g o K,E l l i s o n KE,e t a l.ROS 1immunohistochemistry among major genotypes of non-smallcell lung cancer[J].Clin lung Cancer,2015,16(2):106-111.
[47]Jin Y,Sun PL,Park SY,et al.Frequent aerogenous spread with decreased E-cadherin expression of ROS1-rearranged lung cancer predicts poor disease-free survival[J].Lung Cancer,2015,89(3):343-349.
[48]Gainor JF,Shaw AT.Novel targets in non-small cell lung cancer:ROS1 and RET fusions[J].Oncologist,2013,18(7):865-875.
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