Elevated Levels of Certain GEF Proteins Associated with Shorter Progression-Free Survival in Metastatic Colorectal Cancer

Researchers at University of California (UC), San Diego School of Medicine and Moores Cancer Center, together with colleagues in Spain and Germany, have unraveled how elevated levels of particular proteins in cancer cells trigger hyperactivity in other proteins, fueling the growth and spread of a variety of cancers. The findings are published in the February 26, 2016 online publication of Scientific Reports. The open-access article is titled “Prognostic Impact of Modulators of G proteins in Circulating Tumor Cells from Patients with Metastatic Colorectal Cancer.” Specifically, the international team, led by senior author Pradipta Ghosh, MD, Associate Professor at UC San Diego School of Medicine, found that increased levels of expression of some members of a protein family called guanine nucleotide exchange factors (GEFs) triggered unsuspected hyperactivation of G proteins and subsequent progression or metastasis of cancer. The discovery suggests GEFs offer a new and more precise indicator of disease state and prognosis. "We found that elevated expression of each GEF is associated with a shorter progression-free survival in patients with metastatic colorectal cancer," said Dr. Ghosh. "The GEFs fared better as prognostic markers than two well-known markers of cancer progression and the clustering of all GEFs together improved the predictive accuracy of each individual family member." In recent years, circulating tumor cells (CTCs), which are shed from primary tumors into the bloodstream and act as seeds for new tumors taking root in other parts of the body, have become a prognostic and predictive biomarker. The presence of CTCs is used to monitor the efficacy of therapies and to detect early signs of metastasis. But counting CTCs in the bloodstream has limited utility, said Dr. Ghosh.
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