Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer.
Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer.
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DOI：
10.1111/cas.13504
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发表时间：
2018-03
期刊：
影响因子：
5.7
通讯作者：
Katayama R
中科院分区：
文献类型：
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作者：
Katayama R
间变性淋巴瘤激酶（ALK）基因编码一种受体酪氨酸激酶，在多种肿瘤中发现了多种ALK融合基因。在成人中几乎没有可检测到的ALK表达。然而，通过ALK基因重排，产生的ALK融合蛋白异常过表达，并通过融合伴侣中的寡聚化结构域（如卷曲螺旋结构域）二聚化，诱导ALK酪氨酸激酶的异常组成性激活。这导致细胞增殖失调。在3%-5%的非小细胞肺癌中观察到ALK基因重排，已开发出多种ALK抑制剂用于治疗ALK阳性肺癌。在这些抑制剂中，日本有3种（美国有4种）ALK酪氨酸激酶抑制剂（TKI）已获得批准，目前正在临床使用。所有目前获批的ALK-TKI均显示可诱导ALK重排的非小细胞肺癌的显著肿瘤消退;然而，由于几年内获得性耐药，肿瘤不可避免地复发。本文综述了ALK‐ TKI、其耐药机制以及克服耐药的潜在治疗策略。
The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and many kinds of ALK fusion genes have been found in a variety of carcinomas. There is almost no detectable expression of ALK in adults. However, through ALK gene rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and dimerized through the oligomerization domains, such as the coiled‐coil domain, in the fusion partner that induces abnormal constitutive activation of ALK tyrosine kinase. This results in dysregulated cell proliferation. ALK gene rearrangement has been observed in 3%‐5% of non‐small‐cell lung cancers, and multiple ALK inhibitors have been developed for the treatment of ALK‐positive lung cancer. Among those inhibitors, in Japan, 3 (4 in the USA) ALK tyrosine kinase inhibitors (TKIs) have been approved and are currently used in clinics. All of the currently approved ALK‐TKIs have been shown to induce marked tumor regression in ALK‐rearranged non‐small‐cell lung cancer; however, tumors inevitably relapse because of acquired resistance within a few years. This review focuses on ALK‐TKIs, their resistance mechanisms, and the potential therapeutic strategies to overcome resistance.
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影响因子：
82.9
作者：
Hrustanovic G;Olivas V;Pazarentzos E;Tulpule A;Asthana S;Blakely CM;Okimoto RA;Lin L;Neel DS;Sabnis A;Flanagan J;Chan E;Varella-Garcia M;Aisner DL;Vaishnavi A;Ou SH;Collisson EA;Ichihara E;Mack PC;Lovly CM;Karachaliou N;Rosell R;Riess JW;Doebele RC;Bivona TG
通讯作者：
Bivona TG
影响因子：
28.2
作者：
Friboulet L;Li N;Katayama R;Lee CC;Gainor JF;Crystal AS;Michellys PY;Awad MM;Yanagitani N;Kim S;Pferdekamper AC;Li J;Kasibhatla S;Sun F;Sun X;Hua S;McNamara P;Mahmood S;Lockerman EL;Fujita N;Nishio M;Harris JL;Shaw AT;Engelman JA
通讯作者：
Engelman JA
DOI：
10.1158/1078-0432.ccr-14-1511
发表时间：
2014-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Katayama R;Friboulet L;Koike S;Lockerman EL;Khan TM;Gainor JF;Iafrate AJ;Takeuchi K;Taiji M;Okuno Y;Fujita N;Engelman JA;Shaw AT
通讯作者：
Shaw AT
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：
51.1
作者：
Gadgeel, Shirish M.;Gandhi, Leena;Ou, Sai-Hong Ignatius
通讯作者：
Ou, Sai-Hong Ignatius