The Cancer Phenotype is Controlled by a Network of CRGs
Neoplastic progression is associated with profound changes in the gene networks that control the functioning of the cell. Interrogation of these networks by specific gene perturbations thus will be required to understand the development and progression of cancer and to identify intervention targets with inherent cancer cell specificity. The discovery of CRGs provides us with unprecedented access to essential components of the mechanisms mediating the malignant phenotype downstream of cooperating oncogenic mutations. We have preliminary evidence to show that regulation of CRG expression by cooperating oncogenic mutations underlies robust hierarchical organization, thus indicating functional relationships between CRGs. We predict that investigation of CRG network architecture provides a rational path to identification of cancer cell-specific vulnerabilities and thus the rational design of multi-targeted cancer intervention strategies.
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