Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.
Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.
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DOI：
10.1186/s12943-018-0777-1
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发表时间：
2018-02-19
期刊：
影响因子：
37.3
通讯作者：
Shih JY
中科院分区：
文献类型：
--
作者：
Wu SG;Shih JY
诊断和治疗方面的最新进展使治疗肺癌的方法更具针对性。针对特定致癌驱动突变的治疗可以抑制肿瘤的进展，并在临床实践中提供良好的预后。非小细胞肺癌（NSCLC）中表皮生长因子受体（EGFR）的激活突变是EGFR酪氨酸激酶抑制剂（TKIs）治疗的有利预测因素。对于egfr -外显子19缺失或外显子21 Leu858Arg突变的肺癌患者，标准的一线治疗是第一代（吉非替尼、厄洛替尼）或第二代（阿法替尼）TKIs。EGFR TKIs可提高应答率、进展时间和总生存期。不幸的是，EGFR突变肺癌患者在接受EGFR TKI治疗中位数为10 - 14个月后出现疾病进展。第一代和第二代EGFR TKIs获得性耐药的不同机制已被报道。除T790M突变外，对各种获得性耐药机制的最佳治疗尚未明确定义。反复组织活检对探索耐药机制很重要，但有局限性和风险。液体活检是一种有效的替代组织再活检。奥西替尼已被批准用于对EGFR TKI获得性耐药的t790m阳性NSCLC患者。对于其他tki耐药机制，可以考虑联合治疗。此外，免疫疗法在肺癌治疗中的应用也发展迅速。了解和阐明egfr突变型NSCLC耐药机制的生物学原理可以指导未来的药物开发，从而实现更精确的治疗和治疗进展。
Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs. EGFR TKIs improve response rates, time to progression, and overall survival. Unfortunately, patients with EGFR mutant lung cancer develop disease progression after a median of 10 to 14 months on EGFR TKI. Different mechanisms of acquired resistance to first-generation and second-generation EGFR TKIs have been reported. Optimal treatment for the various mechanisms of acquired resistance is not yet clearly defined, except for the T790M mutation. Repeated tissue biopsy is important to explore resistance mechanisms, but it has limitations and risks. Liquid biopsy is a valid alternative to tissue re-biopsy. Osimertinib has been approved for patients with T790M-positive NSCLC with acquired resistance to EGFR TKI. For other TKI-resistant mechanisms, combination therapy may be considered. In addition, the use of immunotherapy in lung cancer treatment has evolved rapidly. Understanding and clarifying the biology of the resistance mechanisms of EGFR-mutant NSCLC could guide future drug development, leading to more precise therapy and advances in treatment.
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影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C
DOI：
10.1158/1078-0432.ccr-11-1468
发表时间：
2011-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chaft JE;Oxnard GR;Sima CS;Kris MG;Miller VA;Riely GJ
通讯作者：
Riely GJ
DOI：
10.1073/pnas.0710370104
发表时间：
2007-12-26
影响因子：
11.1
作者：
Bean, James;Brennan, Cameron;Pao, William
通讯作者：
Pao, William
影响因子：
9.3
作者：
Caswell DR;Swanton C
通讯作者：
Swanton C
影响因子：
3.6
作者：
Alam, Naheed;Gustafson, Karen S.;Dudek, Arkadiusz Z.
通讯作者：
Dudek, Arkadiusz Z.