Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

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Author
McCubrey, James A.; Steelman, Linda S.; Chappell, William H.; Abrams, Stephen L.; Franklin, Richard A.; Montalto, Giuseppe; Cervello, Melchiorre; Libra, Massimo; Candido, Saverio; Malaponte, Graziella; Mazzarino, Maria C.; Fagone, Paolo; Nicoletti, Ferdinando; Bäsecke, Jörg; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Milella, Michele; Tafuri, Agostino; Chiarini, Francesca; Evangelisti, Camilla; Cocco, Lucio; Martelli, Alberto M.
Abstract
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). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.
URI
http://hdl.handle.net/10342/5687
Subject
 Targeted Therapy,; Combination Therapy; Drug Resistance; Cancer Stem Cells; Aging; Senescence; Raf; Akt; PI3K; mTOR 
Date
2012-10
Citation:
APA:
McCubrey, James A., & Steelman, Linda S., & Chappell, William H., & Abrams, Stephen L., & Franklin, Richard A., & Montalto, Giuseppe, & Cervello, Melchiorre, & Libra, Massimo, & Candido, Saverio, & Malaponte, Graziella, & Mazzarino, Maria C., & Fagone, Paolo, & Nicoletti, Ferdinando, & Bäsecke, Jörg, & Mijatovic, Sanja, & Maksimovic-Ivanic, Danijela, & Milella, Michele, & Tafuri, Agostino, & Chiarini, Francesca, & Evangelisti, Camilla, & Cocco, Lucio, & Martelli, Alberto M.. (October 2012). Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance. Oncotarget, (3:10), p.1068-1111. Retrieved from http://hdl.handle.net/10342/5687

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MLA:
McCubrey, James A., and Steelman, Linda S., and Chappell, William H., and Abrams, Stephen L., and Franklin, Richard A., and Montalto, Giuseppe, and Cervello, Melchiorre, and Libra, Massimo, and Candido, Saverio, and Malaponte, Graziella, and Mazzarino, Maria C., and Fagone, Paolo, and Nicoletti, Ferdinando, and Bäsecke, Jörg, and Mijatovic, Sanja, and Maksimovic-Ivanic, Danijela, and Milella, Michele, and Tafuri, Agostino, and Chiarini, Francesca, and Evangelisti, Camilla, and Cocco, Lucio, and Martelli, Alberto M.. "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance". Oncotarget. 3:10. (1068-1111.), October 2012. March 04, 2021. http://hdl.handle.net/10342/5687.
Chicago:
McCubrey, James A. and Steelman, Linda S. and Chappell, William H. and Abrams, Stephen L. and Franklin, Richard A. and Montalto, Giuseppe and Cervello, Melchiorre and Libra, Massimo and Candido, Saverio and Malaponte, Graziella and Mazzarino, Maria C. and Fagone, Paolo and Nicoletti, Ferdinando and Bäsecke, Jörg and Mijatovic, Sanja and Maksimovic-Ivanic, Danijela and Milella, Michele and Tafuri, Agostino and Chiarini, Francesca and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M., "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance," Oncotarget 3, no. 10 (October 2012), http://hdl.handle.net/10342/5687 (accessed March 04, 2021).
AMA:
McCubrey, James A., Steelman, Linda S., Chappell, William H., Abrams, Stephen L., Franklin, Richard A., Montalto, Giuseppe, Cervello, Melchiorre, Libra, Massimo, Candido, Saverio, Malaponte, Graziella, Mazzarino, Maria C., Fagone, Paolo, Nicoletti, Ferdinando, Bäsecke, Jörg, Mijatovic, Sanja, Maksimovic-Ivanic, Danijela, Milella, Michele, Tafuri, Agostino, Chiarini, Francesca, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M.. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance. Oncotarget. October 2012; 3(10) 1068-1111. http://hdl.handle.net/10342/5687. Accessed March 04, 2021.
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