Small Molecule Magmas Inhibitors
Paul T. Jubinsky, MD, PhD
The chance of an individual developing cancer in his/her lifetime is slightly greater than 40%. Unfortunately, the cure rates for many malignancies have not appreciatively improved over the last 10 years. Especially problematic are cancers that respond poorly to initial therapy or recur, and pediatric cancers, which are less common than adult tumors, and underfunded.
Cancer cells differ from normal cells in by their 1) high self-renewal capacity, 2) reduced ability to differentiate or become mature, and 3) inability to respond to the normal signals that regulate growth and survival. These characteristics provide the basis for developing new cancer therapies.
In order to determine genes involved in cell proliferation, differentiation and survival that could be potentially targeted for cancer treatment, we stimulated a myeloid cell line with granulocyte-macrophage colony stimulating factor, a growth stimulator and survival factor. Several genes whose mRNA increased rapidly (early response genes) were identified by differential display. A novel gene not previously discovered was further characterized. We named the gene Magmas for mitochondrial associated granulocyte-macrophage colony stimulating factor-signaling molecule. Magmas, among the most highly conserved genes, is present in all organisms except bacteria and is essential for survival. Northern and Western blots of cell extracts showed that Magmas mRNA and protein levels increased in response to growth factors.