Oncogenic K-ras “addiction” and synthetic lethality
Open Access
- 1 September 2009
- journal article
- Published by Taylor & Francis Ltd in Cell Cycle
- Vol. 8 (17), 2676-2678
- https://doi.org/10.4161/cc.8.17.9336
Abstract
Mutational activation of the K-ras gene is a frequent oncogenic event in human cancers, associated with poor clinical prognosis and resistance to treatment. Despite efforts to develop therapeutics that target K-ras or its downstream effector molecules, clinical benefit in this setting has not yet been achieved. An alternative approach to K-ras mutant cancers involves the identification of genes that selectively drive the maintenance of tumors that are “addicted” to or dependent on mutant K-ras. Disruption of these genes would result in “synthetic lethality” specifically in cancer cells driven by mutant K-ras, thereby potentially sparing non-tumor cells. Through this approach, three recent reports have identified PLK1, STK33, SYK, RON and integrin β6 as previously unappreciated pharmacologically tractable targets in the setting of K-ras activation, which drive growth and survival selectively in K-ras-dependent cancer cells.Keywords
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