In a paper in the journal Nature, available online May 25, University of Rochester team has discovered a novel class of genes they believe will lead to a greater understanding of cancer cell function and the next generation of effective and less harmful therapies for patients. They describe the discovery of approximately 100 genes that work downstream of known cancer-causing mutations, providing a host of new opportunities for intervention. Targeted cancer therapy – such as the drug Gleevec that works for patients with certain types of leukemia and gastrointestinal tumors – is based on a keen understanding of the architecture of cancer. Much has been learned in the past several years, but what has been lacking is a clear roadmap leading to dozens of new molecular targets.
Twenty-five years ago Land was among the first scientists to discover that malignant cell transformation required multiple mutations in distinct cancer genes. Ever since, he has been studying the cooperative nature of this process and the inner workings of cancer cell function. His research group began testing, at the genomic scale, a prediction that genes responding synergistically to cooperating oncogenic mutations might act as the “drivers” toward malignancy. It now appears that this hunch has paid off.
Research group termed those 100 genes CRGs, for “cooperation response genes.” By studying a subset of the CRGs, researchers also found that 14 of 24 CRGs were essential to tumor formation. In contrast, only one of 14 genes responding in a non-synergistic manner (non-CRGs) had a similar effect. The significance of Ras and p53, and by association the CRGs, is enormous. Ras and p53 are implicated in about half of all cancers. When p53, a tumor-suppressor gene, loses its function, and when Ras becomes hyperactive, both genes play major roles in promoting uncontrolled growth of colon, pancreas and lung cancers.
Ras activation and p53 loss-of-function cooperatively work together through the CRGs, which encode proteins that regulate cell signaling, cell metabolism, self-renewal, cell differentiation and cell death. Much more work needs to be done to explore how our findings may lead to successful targeting of various cancer types and cancer stem cells. via Univ of Rochester Medical School.
Twenty-five years ago Land was among the first scientists to discover that malignant cell transformation required multiple mutations in distinct cancer genes. Ever since, he has been studying the cooperative nature of this process and the inner workings of cancer cell function. His research group began testing, at the genomic scale, a prediction that genes responding synergistically to cooperating oncogenic mutations might act as the “drivers” toward malignancy. It now appears that this hunch has paid off.
Research group termed those 100 genes CRGs, for “cooperation response genes.” By studying a subset of the CRGs, researchers also found that 14 of 24 CRGs were essential to tumor formation. In contrast, only one of 14 genes responding in a non-synergistic manner (non-CRGs) had a similar effect. The significance of Ras and p53, and by association the CRGs, is enormous. Ras and p53 are implicated in about half of all cancers. When p53, a tumor-suppressor gene, loses its function, and when Ras becomes hyperactive, both genes play major roles in promoting uncontrolled growth of colon, pancreas and lung cancers.
Ras activation and p53 loss-of-function cooperatively work together through the CRGs, which encode proteins that regulate cell signaling, cell metabolism, self-renewal, cell differentiation and cell death. Much more work needs to be done to explore how our findings may lead to successful targeting of various cancer types and cancer stem cells. via Univ of Rochester Medical School.
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