Coregulation of pathways in lung cancer patients with EGFR mutation: therapeutic opportunities.
Coregulation of pathways in lung cancer patients with EGFR mutation: therapeutic opportunities.
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DOI：
10.1038/s41416-021-01519-2
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发表时间：
2021-12
影响因子：
8.8
通讯作者：
Santarpia M
中科院分区：
文献类型：
--
作者：
Rosell R;Cardona AF;Arrieta O;Aguilar A;Ito M;Pedraz C;Codony-Servat J;Santarpia M
肺腺癌中的表皮生长因子受体（EGFR）突变是一类常见的驱动突变。单一EGFR酪氨酸激酶抑制剂（TKI）提供了大量的临床获益，但几乎没有放射学完全缓解。患者总是进展，尽管通过治疗后治疗，包括EGFR TKI，化疗或其他程序，生存期可达数年。临床上一直致力于管理EGFR TKI耐药突变的获得;然而，临床试验中尚未考虑癌症演变的基本原则。多年来，有证据表明，快速适应机制的阻力选择性单一疗法，提出了几个两难的医生。严格遵守非小细胞肺癌（NSCLC）指南对于解决EGFR突变型肺腺癌患者的临床进展并不总是实用的。本综述的目的是强调导致治疗诱导的EGFR TKI耐药的调控机制和信号通路。它提出了靶向EGFR的组合疗法，以及EGFR突变型NSCLC的潜在机制，提醒读者注意可能导致更深入和更持久反应的临床机会。分子重编程导致EGFR TKI耐药，汇编的信息与理解EGFR突变型NSCLC中新的联合靶向策略的开发相关。
Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma are a frequent class of driver mutations. Single EGFR tyrosine kinase inhibitor (TKI) provides substantial clinical benefit, but almost nil radiographic complete responses. Patients invariably progress, although survival can reach several years with post-treatment therapies, including EGFR TKIs, chemotherapy or other procedures. Endeavours have been clinically oriented to manage the acquisition of EGFR TKI-resistant mutations; however, basic principles on cancer evolution have not been considered in clinical trials. For years, evidence has displayed rapidly adaptive mechanisms of resistance to selective monotherapy, posing several dilemmas for the practitioner. Strict adherence to non-small cell lung cancer (NSCLC) guidelines is not always practical for addressing the clinical progression that EGFR-mutant lung adenocarcinoma patients suffer. The purpose of this review is to highlight regulatory mechanisms and signalling pathways that cause therapy-induced resistance to EGFR TKIs. It suggests combinatorial therapies that target EGFR, as well as potential mechanisms underlying EGFR-mutant NSCLC, alerting the reader to clinical opportunities that may lead to a deeper and more durable response. Molecular reprogramming contributes to EGFR TKI resistance, and the compiled information is relevant in understanding the development of new combined targeted strategies in EGFR-mutant NSCLC.
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影响因子：
30.8
作者：
Blakely CM;Watkins TBK;Wu W;Gini B;Chabon JJ;McCoach CE;McGranahan N;Wilson GA;Birkbak NJ;Olivas VR;Rotow J;Maynard A;Wang V;Gubens MA;Banks KC;Lanman RB;Caulin AF;St John J;Cordero AR;Giannikopoulos P;Simmons AD;Mack PC;Gandara DR;Husain H;Doebele RC;Riess JW;Diehn M;Swanton C;Bivona TG
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Bivona TG
影响因子：
64.8
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Ben-David U
影响因子：
16.6
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影响因子：
82.9
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影响因子：
50.3
作者：
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通讯作者：
Baselga J