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Gene signature critical to cancer phenotype as a paradigm for anticancer drug discovery

E R Sampson1, H R McMurray, D C Hassane

  • 1Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.

Oncogene
|September 12, 2012
PubMed

Insights

Researchers identified

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant cell transformation involves complex gene deregulation, posing challenges for cancer intervention.
  • Cooperating oncogenic mutations drive synergistic gene deregulation, leading to a malignant phenotype.
  • Cooperation response genes (CRGs) are critical for the cancer phenotype and its malignant state.

Purpose of the Study:

  • To define genes and pathways essential for regulating the malignant phenotype.
  • To investigate the role of CRGs in anticancer drug activity.
  • To explore CRG signatures for novel cancer drug discovery.

Main Methods:

  • Described a novel strategy focusing on genes synergistically deregulated by cooperating oncogenic mutations.
  • Analyzed CRGs for their enrichment in genes critical for the cancer phenotype.
  • Tested the ability of anticancer agents to antagonize CRG expression profiles.

Main Results:

  • CRGs are highly enriched for genes critical to the cancer phenotype, suggesting a causal role.
  • CRGs play an essential role in drug-mediated anticancer activity.
  • Anticancer agents can be identified by their ability to antagonize CRG expression profiles.

Conclusions:

  • CRGs are causally linked to the malignant state.
  • CRGs are essential for anticancer drug efficacy.
  • CRG signatures offer a novel approach for cancer drug discovery and understanding drug mechanisms.

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