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Cancer Gene Plays Bigger Role in Regulation Than Previously Thought

Scripps Institute study shows that disabling Notch 1 leads to rise in cell death (August 30)

A well-known cancer-causing gene implicated in a number of malignancies plays a far more critical role in non-small cell lung cancer, the most common form of the disease, than previously thought. The findings, from the Scripps Research Institute, establish the oncogene, Notch 1, as a critical regulator of lung cancer tumor growth. That’s an important development because it could be vital for the design of potentially new therapeutic strategies for a group of patients who represent almost half of non-small cell lung cancer cases.

In the study, published online by Cancer Research, the scientists found that the presence of the oncogene is required for survival of cancer cells. In both cell and animal model studies, disabling Notch 1 leads to a rise in cancer cell death.

“While Notch signaling has emerged as an important target in many types of cancer, current methodologies that target that pathway affect all members of the Notch family, and this has been associated with toxicity,” said Joseph Kissil, a TSRI associate professor who led the study. “We were able to identify Notch 1 as the critical oncogene to target, at least in a common form of lung cancer.”

The new findings show that Notch 1 is required for initial tumor growth, as it represses p53, a well-known tumor suppressor protein that has been called the genome’s guardian because of its role in preventing mutations. The p53 protein can repair damaged cells or force them to die through apoptosis—programmed cell death.

These findings provide important clinical insights into the correlation between Notch1 activity and the poor prognosis of non-small cell lung cancer patients who carry the non-mutated form of the p53 gene.

“If you look at lung cancer patient populations, Notch signaling alone isn’t a prognostic indicator, but if you look at p53-positive patients it is,” Kissil said.

Source: Scripps Research Institute

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