Targeting cancer with small molecule kinase inhibitors

@article{Zhang2009TargetingCW,
  title={Targeting cancer with small molecule kinase inhibitors},
  author={Jianming Zhang and Priscilla L. Yang and Nathanael S. Gray},
  journal={Nature Reviews Cancer},
  year={2009},
  volume={9},
  pages={28-39}
}
Deregulation of kinase activity has emerged as a major mechanism by which cancer cells evade normal physiological constraints on growth and survival. To date, 11 kinase inhibitors have received US Food and Drug Administration approval as cancer treatments, and there are considerable efforts to develop selective small molecule inhibitors for a host of other kinases that are implicated in cancer and other diseases. Herein we discuss the current challenges in the field, such as designing selective… 

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An overview of the novel targets, biological processes and disease areas that kinase-targeting small molecules are being developed against, highlight the associated challenges and assess the strategies and technologies that are enabling efficient generation of highly optimized kinase inhibitors are provided.

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The most recently identified molecular mechanisms that mediate acquired resistance to tyrosine kinase inhibitors are presented through the use of in vitro models or the analysis of patient samples to help design better therapies that prevent and overcome resistance to treatment in cancer patients.

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It is illustrated that although certain kinase targets may be pharmacologically easily tractable, a better understanding of the regulation and biology of the targets is required to generate drugs that are efficacious in cancer patients.
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