Literature DB >> 23953481

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

Ruth Nussinov1, Chung-Jung Tsai, Carla Mattos.   

Abstract

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.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

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

Mesh:

Substances:

Year:  2013        PMID: 23953481     DOI: 10.1016/j.molmed.2013.07.009

Source DB:  PubMed          Journal:  Trends Mol Med        ISSN: 1471-4914            Impact factor:   11.951


  29 in total

Review 1.  Intracellular and intercellular signaling networks in cancer initiation, development and precision anti-cancer therapy: RAS acts as contextual signaling hub.

Authors:  Peter Csermely; Tamás Korcsmáros; Ruth Nussinov
Journal:  Semin Cell Dev Biol       Date:  2016-07-06       Impact factor: 7.727

Review 2.  Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view.

Authors:  Shaoyong Lu; Hyunbum Jang; Shuo Gu; Jian Zhang; Ruth Nussinov
Journal:  Chem Soc Rev       Date:  2016-07-11       Impact factor: 54.564

Review 3.  Searching for the Chokehold of NRAS Mutant Melanoma.

Authors:  Christian Posch; Igor Vujic; Babak Monshi; Martina Sanlorenzo; Felix Weihsengruber; Klemens Rappersberger; Susana Ortiz-Urda
Journal:  J Invest Dermatol       Date:  2016-05-07       Impact factor: 8.551

4.  The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases.

Authors:  Desirée García-Torres; Carol A Fierke
Journal:  J Biol Chem       Date:  2019-06-13       Impact factor: 5.157

Review 5.  Inhibition of Nonfunctional Ras.

Authors:  Ruth Nussinov; Hyunbum Jang; Attila Gursoy; Ozlem Keskin; Vadim Gaponenko
Journal:  Cell Chem Biol       Date:  2021-01-12       Impact factor: 8.116

Review 6.  Oncogenic Ras Isoforms Signaling Specificity at the Membrane.

Authors:  Ruth Nussinov; Chung-Jung Tsai; Hyunbum Jang
Journal:  Cancer Res       Date:  2017-12-22       Impact factor: 12.701

7.  The free energy landscape in translational science: how can somatic mutations result in constitutive oncogenic activation?

Authors:  Chung-Jung Tsai; Ruth Nussinov
Journal:  Phys Chem Chem Phys       Date:  2014-01-21       Impact factor: 3.676

8.  Computational Modeling Reveals that Signaling Lipids Modulate the Orientation of K-Ras4A at the Membrane Reflecting Protein Topology.

Authors:  Zhen-Lu Li; Matthias Buck
Journal:  Structure       Date:  2017-03-09       Impact factor: 5.006

9.  SmgGDS-558 regulates the cell cycle in pancreatic, non-small cell lung, and breast cancers.

Authors:  Nathan J Schuld; Andrew D Hauser; Adam J Gastonguay; Jessica M Wilson; Ellen L Lorimer; Carol L Williams
Journal:  Cell Cycle       Date:  2014-01-16       Impact factor: 4.534

Review 10.  A New View of Ras Isoforms in Cancers.

Authors:  Ruth Nussinov; Chung-Jung Tsai; Mayukh Chakrabarti; Hyunbum Jang
Journal:  Cancer Res       Date:  2015-12-10       Impact factor: 12.701

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