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

Ruth Nussinov1, Chung-Jung Tsai, Carla Mattos

  • 1Basic Research Program, SAIC-Frederick, Inc., Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Sackler Institute of Molecular Medicine, Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Trends in Molecular Medicine
|August 20, 2013
PubMed

Insights

Targeting Ras mutations in tumors is challenging. Pathway drug cocktails, by hitting parallel pathways, offer a promising therapeutic strategy, especially when guided by structural pathway networks.

Area of Science:

  • Oncology
  • Molecular Biology
  • Systems Biology

Background:

  • Ras mutations are common drivers of tumorigenesis and are notoriously difficult to treat with single-agent therapies.
  • Existing combination therapies targeting the Ras protein or its direct pathway have shown limited success.
  • The complexity of signaling networks necessitates a deeper understanding for effective therapeutic intervention.

Purpose of the Study:

  • To highlight the potential of 'pathway drug cocktails' for treating Ras-mutated tumors.
  • To emphasize the need for a classified repertoire of pathway combinations.
  • To underscore the importance of structural signaling pathway networks for advancing therapeutic platforms.

Main Methods:

  • Leveraging structural knowledge of signaling pathways.
  • Integrating pathway networks with functional and systems-level clinical data.
  • Analyzing the interrelationship between Ras mutations and rewiring of the Ras network.

Main Results:

  • Pathway drug cocktails show promise by targeting parallel pathways, offering a more effective approach than single-target drugs.
  • Structural pathway networks are crucial for classifying and exploiting combination therapies.
  • Understanding network rewiring can reveal vulnerabilities in tumorigenesis driven by Ras mutations.

Conclusions:

  • Pathway drug cocktails represent a promising therapeutic paradigm for Ras-mutated cancers.
  • The development of a classified repertoire of pathway combinations, informed by structural network data, is essential.
  • This approach can be extended to target other signaling proteins implicated in cancer.
Keywords:
cancerclassificationdrug discoveryoncogenic mutationsparallel pathwaysstructures

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