A genome-wide RNAi screening tool was used to identify a dozen genes that affect the function of a crucial protein necessary for glioma cells to grow. In addition, the key pathway appears in laboratory cultures and mouse models to be susceptible to two cancer drugs already in use for other types of cancer.
A hallmark of cancer is uncontrolled cell growth, often caused by overexpression of genes that help cells survive, or underexpression of those genes that induce normal cell death. Genes that are expressed highly in cancer cells and are essential for their survival are attractive targets for drug therapy.
University of Massachusetts Medical School (Worcester, MA, USA) Prof. Michael R. Green, M.D., Ph.D., and colleagues revealed the essential cellular survival pathway, CREB3L2-ATF5-MCL1, in malignant glioma. The team identified novel genes that regulate the expression of a transcription factor called ATF5 in malignant glioma cells.
The discovery of at least one previously unknown genetic pathway that appears to regulate this key transcription factor, and the subsequent determination that the cancer drugs sorafenib and temozolomide inhibit glioma growth, indicate new possibilities for potential therapeutics.
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