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

Trends Mol Med. 2013 Nov;19(11):695-704. doi: 10.1016/j.molmed.2013.07.009. Epub 2013 Aug 15.


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.

Keywords: cancer; classification; drug discovery; oncogenic mutations; parallel pathways; structures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Therapy, Combination
  • Humans
  • Neoplasms / diet therapy
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Signal Transduction / drug effects*
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / genetics
  • ras Proteins / metabolism*


  • ras Proteins