The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions.
The Current Landscape of Anaplastic Lymphoma Kinase (ALK) in Non-Small Cell Lung Cancer: Emerging Treatment Paradigms and Future Directions.
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DOI：
10.1007/s11523-017-0526-1
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发表时间：
2017-12
影响因子：
5.4
通讯作者：
Gadgeel S
中科院分区：
文献类型：
--
作者：
Qin A;Gadgeel S
间变性淋巴瘤激酶(ALK)的致瘤重排占所有非小细胞肺癌(NSCLC)的3-7%。靶向酪氨酸激酶抑制剂(TKIs)的治疗已显示出令人印象深刻的临床反应。Crizotinib是第一个被批准用于ALK重排NSCLC一线治疗的药物，因为它在有效率、有效时间和无进展生存期方面优于化疗。然而，最终所有患者在Crizotinib治疗上都取得了进展，其中中枢神经系统(CNS)是最常见的部位，这推动了更有效的下一代ALK抑制剂的开发。目前，Ceritinib、Alectinib和Brigatinib都被批准用于对Crizotinib进展或不耐受的二线治疗。关于开始使用第二代ALK抑制剂作为一线治疗是否是更好的治疗范例的调查，导致了Ceritinib作为初始治疗的批准。阿莱替尼作为一线治疗也显示出令人印象深刻的结果，最近在两项将其与克里佐替尼进行比较的大型随机研究中报道了这一结果。有必要更好地了解ALK抑制剂耐药的驱动因素和潜在机制。虽然已经确定了特定的突变，但目前只有有限的证据表明，特定突变的确定应该影响下一个ALK抑制剂的选择。对TKI难治性患者的最佳治疗方案也不清楚，尽管有一些证据表明，这些患者对检查点抑制剂没有反应，对化疗可能有更好的反应。与其他类别的药物联合治疗可能有助于克服耐药机制，应进一步研究。
Tumorigenic rearrangements in anaplastic lymphoma kinase (ALK) account for 3–7% of all non-small cell lung cancers (NSCLC). Treatment with targeted tyrosine kinase inhibitors (TKIs) has shown impressive clinical responses. Crizotinib was the first agent approved for front-line therapy of ALK-rearranged NSCLC after it demonstrated superiority to chemotherapy in response rate, duration of response, and progression-free survival. However, eventually all patients progress on crizotinib therapy, with the central nervous system (CNS) being the most common site, which served as the impetus for the development of more potent next-generation ALK inhibitors. Currently, ceritinib, alectinib, and brigatinib are all approved for second-line therapy after progression on or intolerance to crizotinib. Investigations into whether the initiation of a second-generation ALK inhibitor as first-line therapy is the superior treatment paradigm has resulted in the approval of ceritinib as initial therapy. Alectinib has also shown impressive results as front-line therapy, as recently reported in two large randomized studies that compared it to crizotinib. There is a significant need to better understand the drivers of and mechanisms underlying resistance to ALK inhibitors. While specific mutations have been identified, there is currently only limited evidence that the identification of specific mutations should impact selection of the next ALK inhibitor. The best treatment option for patients who become TKI refractory is also unclear, though there is some evidence to suggests that these patients are not responsive to checkpoint inhibitors and may respond better to chemotherapy. Combination therapy with other classes of agents may help to overcome resistance mechanisms and should be investigated further.
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影响因子：
3.9
作者：
Abdelhamed S;Ogura K;Yokoyama S;Saiki I;Hayakawa Y
通讯作者：
Hayakawa Y
DOI：
10.1158/1078-0432.ccr-15-3101
发表时间：
2016-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gainor JF;Shaw AT;Sequist LV;Fu X;Azzoli CG;Piotrowska Z;Huynh TG;Zhao L;Fulton L;Schultz KR;Howe E;Farago AF;Sullivan RJ;Stone JR;Digumarthy S;Moran T;Hata AN;Yagi Y;Yeap BY;Engelman JA;Mino-Kenudson M
通讯作者：
Mino-Kenudson M
影响因子：
20.4
作者：
Cho, Byoung Chul;Kim, Dong-Wan;Wrona, Anna
通讯作者：
Wrona, Anna
影响因子：
4.1
作者：
Abel, Haley J.;Al-Kateb, Hussam;Duncavage, Eric J.
通讯作者：
Duncavage, Eric J.
影响因子：
45.3
作者：
Kim, Dong-Wan;Tiseo, Marcello;Camidge, D. Ross
通讯作者：
Camidge, D. Ross