Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs

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• 作者：Richard Bayliss ; Jene Choi ; Dean A. Fennell…
• 关键词：Fusion ; Oncogene ; Lung cancer ; Kinase ; Structural biology
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：73
• 期：6
• 页码：1209-1224
• 全文大小：3,110 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

A fusion between the EML4 (echinoderm microtubule-associated protein-like) and ALK (anaplastic lymphoma kinase) genes was identified in non-small cell lung cancer (NSCLC) in 2007 and there has been rapid progress in applying this knowledge to the benefit of patients. However, we have a poor understanding of EML4 and ALK biology and there are many challenges to devising the optimal strategy for treating EML4-ALK NSCLC patients. In this review, we describe the biology of EML4 and ALK, explain the main features of EML4-ALK fusion proteins and outline the therapies that target EML4-ALK. In particular, we highlight the recent advances in our understanding of the structures of EML proteins, describe the molecular mechanisms of resistance to ALK inhibitors and assess current thinking about combinations of ALK drugs with inhibitors that target other kinases or Hsp90.