Novel therapeutic targets in non-small cell lung cancer
Novel therapeutic targets in non-small cell lung cancer
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DOI：
10.1016/j.coph.2013.03.010
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发表时间：
2013-06-01
影响因子：
4
通讯作者：
Watkins, D. Neil
中科院分区：
文献类型：
--
作者：
Alamgeer, Muhammad;Ganju, Vinod;Watkins, D. Neil
致癌驱动突变在肺癌中经常发生，并在癌变中发挥作用。这些突变通常与不同的临床和组织学特征相关，是抗癌治疗的有吸引力的靶点。最近，一些基于特异性和互斥的遗传失调的非小细胞肺癌的分子不同表型已经被描述。表皮生长因子受体（EGFR）突变和间变性淋巴瘤激酶（ALK）基因重排等靶点分别成功地靶向了EGFR酪氨酸激酶抑制剂（TKIs）和克唑替尼。目前正在开发更多涉及ROS、c-MET、FGFR、mTOR、IGFR和RET等基因的特定驱动突变抑制剂。然而，针对K-RAS等一些突变基因的努力一直没有成功。此外，对最初有效治疗的获得性耐药的新挑战正在成为另一个主要问题。本文综述了近年来新型分子靶点的研究进展，并对其前景进行了展望。
Oncogenic driver mutations frequently occur in lung cancer and play role in carcinogenesis. These mutations are usually associated with distinct clinical and histological features and are attractive targets for anticancer therapy. Recently, several molecularly distinct phenotypes of NSCLC based on specific and mutually exclusive genetic derangements have been described. Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively. Many more inhibitors of specific driver mutations involving genes like ROS, c-MET, FGFR, mTOR, IGFR and RET are currently under development. However, efforts to target some mutated genes like K-RAS have been unsuccessful. Moreover, the emerging challenge of acquired resistance to initially effective therapy is becoming another major concern. In this review recent data on novel molecular targets and their future prospects are discussed.