A comprehensive review of protein kinase inhibitors for cancer therapy.
A comprehensive review of protein kinase inhibitors for cancer therapy.
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DOI：
10.1080/14737140.2018.1527688
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发表时间：
2018-12
影响因子：
3.3
通讯作者：
Mahadevan D
中科院分区：
文献类型：
--
作者：
Kannaiyan R;Mahadevan D
蛋白激酶参与各种细胞功能，包括代谢、细胞周期调节、存活和分化。蛋白激酶的失调与各种致癌过程有关。蛋白激酶抑制剂在癌症治疗中的出现导致了我们如何治疗癌症的范式转变。在过去的几十年中，有几种蛋白激酶抑制剂已被FDA批准。本文综述了截至2017年12月FDA批准的蛋白激酶抑制剂对已知致癌蛋白激酶的临床获益和副作用。在PubMed中检索并讨论了相应致癌蛋白激酶在致癌和癌症进展中的作用。PubMed检索并讨论了相关和里程碑式的临床试验，主要是导致FDA批准的蛋白激酶抑制剂III期试验。进一步了解癌症的分子起源将有助于我们确定新的靶点，而试图确定可用激酶抑制剂的适当序列的临床试验将更好地利用目前的蛋白激酶抑制剂。此外，在高复发风险患者的辅助治疗中测试这些药物可能会提供一些临床益处。耐药性的产生、副作用和成本是蛋白激酶抑制剂的主要限制，因此了解耐药性的分子机制并设计蛋白激酶抑制剂来抑制耐药性将有助于克服耐药性。最后，国际癌症研究组织与志愿和慈善组织之间的合作可能有助于降低成本。
Protein kinases are involved in various cellular functions including metabolism, cell cycle regulation, survival, and differentiation. Dysregulation of protein kinases is implicated in various processes of carcinogenesis. The advent of protein kinase inhibitors in cancer therapy has led to a paradigm shift in how we treat cancer. There are several protein kinase inhibitors that have been approved by FDA in the last few decades. This article provides a review of the clinical benefits and side effect profiles of FDA approved protein kinase inhibitors as of December 2017 for the well-known oncogenic protein kinases. The role of the respective oncogenic protein kinases in carcinogenesis and cancer progression were searched in PubMed and discussed. The relevant and landmark clinical trials mostly phase III trials of protein kinase inhibitors leading up to the FDA approval were PubMed searched and discussed. Further understanding of the molecular origin of cancers would help us identify new targets, while clinical trials trying to identify the appropriate sequence of available kinase inhibitor would make better use of current protein kinase inhibitor armamentarium. Also, testing these drugs in the adjuvant setting in patients with high risk of recurrence might offer some clinical benefit. Development of resistance, side effects and cost are major limitations of protein kinase inhibitors, therefore understanding of the molecular mechanisms of resistance and designing protein kinase inhibitors to obviate the resistance would help overcome the resistance. Finally, collaboration between international organizations for cancer research and voluntary and charity organizations might help reduce the cost.
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DOI：
10.1056/nejmoa1510016
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
通讯作者：
METEOR Investigators
影响因子：
168.9
作者：
Brose, Marcia S.;Nutting, Christopher M.;Jarzab, Barbara;Elisei, Rossella;Siena, Salvatore;Bastholt, Lars;de la Fouchardiere, Christelle;Pacini, Furio;Paschke, Ralf;Shong, Young Kee;Sherman, Steven I.;Smit, Johannes W. A.;Chung, John;Kappeler, Christian;Pena, Carol;Molnar, Istvan;Schlumberger, Martin J.
通讯作者：
Schlumberger, Martin J.
影响因子：
168.9
作者：
Bruix, Jordi;Qin, Shukui;Han, Guohong
通讯作者：
Han, Guohong
索拉非尼对亚太地区晚期肝细胞癌患者的疗效和安全性：一项 III 期随机、双盲、安慰剂对照试验
影响因子：
51.1
作者：
Cheng, Ann-Lii;Kang, Yoon-Koo;Guan, Zhongzhen
通讯作者：
Guan, Zhongzhen
DOI：
10.1016/s0140-6736(12)61857-1
发表时间：
2013-01-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Demetri GD;Reichardt P;Kang YK;Blay JY;Rutkowski P;Gelderblom H;Hohenberger P;Leahy M;von Mehren M;Joensuu H;Badalamenti G;Blackstein M;Le Cesne A;Schöffski P;Maki RG;Bauer S;Nguyen BB;Xu J;Nishida T;Chung J;Kappeler C;Kuss I;Laurent D;Casali PG;GRID study investigators
通讯作者：
GRID study investigators