Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response
McCubrey, James A.; Steelman, Linda S.; Chappell, William H.; Abrams, Stephen L.; Montalto, Giuseppe; Cervello, Melchiorre; Nicoletti, Ferdinando; Fagone, Paolo; Malaponte, Grazia; Mazzarino, Maria C.; Candido, Saverio; Libra, Massimo; BÃ¤secke, JÃ¶rg; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Milella, Michele; Tafuri, Agostino; Cocco, Lucio; Evangelisti, Camilla; Chiarini, Francesca; Martelli, Alberto M.
The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5, PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and TSC2 may also be activated/inactivated by mutations or epigenetic silencing. Upstream mutations in one signaling pathway or even in downstream components of the same pathway can alter the sensitivity of the cells to certain small molecule inhibitors. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of components of these cascades can contribute to: resistance to other pathway inhibitors, chemotherapeutic drug resistance, premature aging as well as other diseases. This review will first describe these pathways and discuss how genetic mutations and epigenetic alterations can result in resistance to various inhibitors.
McCubrey, James A., & Steelman, Linda S., & Chappell, William H., & Abrams, Stephen L., & Montalto, Giuseppe, & Cervello, Melchiorre, & Nicoletti, Ferdinando, & Fagone, Paolo, & Malaponte, Grazia, & Mazzarino, Maria C., & Candido, Saverio, & Libra, Massimo, & BÃ¤secke, JÃ¶rg, & Mijatovic, Sanja, & Maksimovic-Ivanic, Danijela, & Milella, Michele, & Tafuri, Agostino, & Cocco, Lucio, & Evangelisti, Camilla, & Chiarini, Francesca, & Martelli, Alberto M.. (September 2012). Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response. Oncotarget, 3(9), 954- 987. Retrieved from http://hdl.handle.net/10342/5658
McCubrey, James A., and Steelman, Linda S., and Chappell, William H., and Abrams, Stephen L., and Montalto, Giuseppe, and Cervello, Melchiorre, and Nicoletti, Ferdinando, and Fagone, Paolo, and Malaponte, Grazia, and Mazzarino, Maria C., and Candido, Saverio, and Libra, Massimo, and BÃ¤secke, JÃ¶rg, and Mijatovic, Sanja, and Maksimovic-Ivanic, Danijela, and Milella, Michele, and Tafuri, Agostino, and Cocco, Lucio, and Evangelisti, Camilla, and Chiarini, Francesca, and Martelli, Alberto M.. "Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response". Oncotarget. 3:9. (954-987), September 2012. October 20, 2018. http://hdl.handle.net/10342/5658.
McCubrey, James A. and Steelman, Linda S. and Chappell, William H. and Abrams, Stephen L. and Montalto, Giuseppe and Cervello, Melchiorre and Nicoletti, Ferdinando and Fagone, Paolo and Malaponte, Grazia and Mazzarino, Maria C. and Candido, Saverio and Libra, Massimo and BÃ¤secke, JÃ¶rg and Mijatovic, Sanja and Maksimovic-Ivanic, Danijela and Milella, Michele and Tafuri, Agostino and Cocco, Lucio and Evangelisti, Camilla and Chiarini, Francesca and Martelli, Alberto M., "Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response," Oncotarget 3, no. 9 (September 2012), http://hdl.handle.net/10342/5658 (accessed October 20, 2018).
McCubrey, James A., Steelman, Linda S., Chappell, William H., Abrams, Stephen L., Montalto, Giuseppe, Cervello, Melchiorre, Nicoletti, Ferdinando, Fagone, Paolo, Malaponte, Grazia, Mazzarino, Maria C., Candido, Saverio, Libra, Massimo, BÃ¤secke, JÃ¶rg, Mijatovic, Sanja, Maksimovic-Ivanic, Danijela, Milella, Michele, Tafuri, Agostino, Cocco, Lucio, Evangelisti, Camilla, Chiarini, Francesca, Martelli, Alberto M.. Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response. Oncotarget. September 2012; 3(9): 954-987. http://hdl.handle.net/10342/5658. Accessed October 20, 2018.