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'Pathway drug cocktail': targeting Ras signaling based on structural pathways

期刊

TRENDS IN MOLECULAR MEDICINE
卷 19, 期 11, 页码 695-704

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2013.07.009

关键词

cancer; drug discovery; parallel pathways; classification; structures; oncogenic mutations

资金

  1. National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E]
  2. Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
  3. extramural program [R56 CA096867]

向作者/读者索取更多资源

Tumors bearing Ras mutations are notoriously difficult to treat. Drug combinations targeting the Ras protein or its pathway have also not met with success. 'Pathway drug cocktails', which are combinations aiming at parallel pathways, appear more promising; however, to be usefully exploited, a repertoire of classified pathway combinations is desirable. This challenge would be facilitated by the availability of the structural network of signaling pathways. When integrated with functional and systems level clinical data, they can be powerful in advancing novel therapeutic platforms. Based on structural knowledge, drug cocktails may tear into multiple cellular processes that drive tumorigenesis, and help in deciphering the interrelationship between Ras mutations and the rewired Ras network. The pathway drug cocktail paradigm can be applied to other signaling protein targets.

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