An oncogene is a kind of abnormal gene that predisposes cells to develop into cancers. Unlike normal genes, oncogenes are altered in a way that keeps them stuck in a state of constant activity. That uninterrupted action helps drive the uncontrolled growth that underlies tumors. One measure scientists take to inhibit this process is that small inhibitory RNAs are designated for silencing oncogenes.
The activation of oncogenes involves genetic changes to cellular proto-oncogenes. The consequence of these genetic alterations is to confer a growth advantage to the cell. Three genetic mechanisms activate oncogenes in human neoplasms: mutation, gene amplification, and chromosome rearrangements. These mechanisms result in either an alteration of proto-oncogene structure or an increase in proto-oncogene expression. Because neoplasia is a multistep process, more than one of these mechanisms often contribute to the genesis of human tumors by altering a number of cancer-associated genes.
Against potential Achilles’ heel in the oncogene
A XBP1 gene implicated in progression and relapse of deadly breast cancer finding points to potential Achilles’ heel in triple negative breast cancer(TNBC), and targeting this gene may be a new approach to treating the disease. Investigators find that interactions between XBP1 and another transcriptional regulator, HIF1-alpha, spurs the cancer-driving proteins. Silencing XBP1 in the TNBC cell lines reduces the tumor cells’ growth and other behaviors typical of metastasis.
Another study shows that a critical gene called oncogene is turned off by RNA interference, and it increases survival rates in mice suffering from glioblastoma. The therapeutic, based on nanotechnology, is nimble enough to cross the blood-brain barrier and get to the brain tumor. Once there, it flips the switch of the oncogene to “off,” silencing the gene.
Reference:
1. Mechanisms of oncogene activation. Holland-Frei Cancer Medicine. 6th edition.
2. XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway. Nature, March 2014 DOI: 10.1038/nature13119
3. Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma. Science Translational Medicine, 2013; 5 (209): 209ra152 DOI: 10.1126/scitranslmed.3006839