A New Targeted Approach to Cancer Therapy
Inhibiting a particular gene specifically attacks many cancer cells.
The Myc oncogene is activated in most human cancers. It achieves its powerful effects because it encodes a transcription factor: Aberrant activation of Myc leads to the coordinated turning on of thousands of other genes, most of which have oncogenic effects. Such genes drive cells to divide, prohibit cell death, and encourage tumor angiogenesis.
A multi-institutional team used RNA interference to identify genes that, when inactivated in the presence of activated Myc, inhibit the development of cancer. The investigators found that inactivating the gene for an enzyme (called SAE1/2) produces defects in the mitotic spindles of cancerous cells triggered to divide by Mycactivation. As a result, the malignant cells die. Other poisons that target mitotic spindles (e.g., taxanes) already are used in cancer therapy. However, these toxins affect mitotic spindles in all cells, whereas inactivation of the SAE1/2 gene affects only cancerous cells in which Myc is activated. This observation appears to be clinically relevant: Metastasis-free survival is longer in human breast cancers in which Myc is activated but SAE1/2 enzyme levels are low.
Comment: Attempts to directly block activation of the Myconcogene have been uniformly unsuccessful. By taking an indirect approach — knocking out a gene that is involved in the pathways through which the Myc oncogene promotes tumor growth — these investigators may have uncovered a new, selectively toxic form of cancer therapy.
Published in Journal Watch General Medicine February 23, 2012
