Geranylgeranyltransferase type I (GGTase-I) has been suggested as a drug target in the treatment of cancer and a host of other diseases. Several inhibitors of GGTase-I (GGTIs) have been synthesized and tested. However, different GGTIs have had very different properties, and a clear picture of the impact of GGTase-I deficiency and GGTI treatment has not yet emerged. Now, in a study appearing in the May 1st issue of the Journal of Clinical Investigation, Martin Bergo and colleagues from Sahlgrenska University Hospital in Sweden describe the impact of GGTase-I deficiency in mammalian cells.
The authors found that, in mice, loss of the gene encoding GGTase-I in cells that would normally produce lung tumors driven by the oncogene K-RAS, resulted in delayed onset and decreased severity of lung cancer in these animals. The findings suggest that, if these results hold true in humans, then inhibiting GGTase-I may be a useful strategy to treat K-RAS--induced malignancies.
In an accompanying commentary, Mark Philips and Adrienne Cox from New York University School of Medicine explore the actions of GGTAse-I and conclude that this new mouse model of disease is likely to be an invaluable tool in assessing the role of GGTase-I in oncogenesis.
Article: GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS--induced lung cancer
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
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