Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health

Chappell, William H.; Steelman, Linda S.; Long, Jacquelyn M.; Kempf, Ruth C.; Abrams, Stephen L.; Franklin, Richard A.; Bäsecke, Jörg; Stivala, Franca; Donia, Marco; Fagone, Paolo; Malaponte, Graziella; Mazzarino, Maria C.; Nicoletti, Ferdinando; Libra, Massimo; Maksimovic-Ivanic, Danijela; Mijatovic, Sanja; Montalto, Giuseppe; Cervello, Melchiorre; Laidler, Piotr; Milella, Michele; Tafuri, Agostino; Bonati, Antonio; Evangelisti, Camilla; Cocco, Lucio; Martelli, Alberto M.; McCubrey, James A.

Author

Chappell, William H.; Steelman, Linda S.; Long, Jacquelyn M.; Kempf, Ruth C.; Abrams, Stephen L.; Franklin, Richard A.; Bäsecke, Jörg; Stivala, Franca; Donia, Marco; Fagone, Paolo; Malaponte, Graziella; Mazzarino, Maria C.; Nicoletti, Ferdinando; Libra, Massimo; Maksimovic-Ivanic, Danijela; Mijatovic, Sanja; Montalto, Giuseppe; Cervello, Melchiorre; Laidler, Piotr; Milella, Michele; Tafuri, Agostino; Bonati, Antonio; Evangelisti, Camilla; Cocco, Lucio; Martelli, Alberto M.; McCubrey, James A.

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/10342/7985

Subject

Targeted Therapy, Combination Therapy, Drug Resistance, Cancer Stem Cells, Aging, Senescence, Raf, Akt, PI3K, mTOR

Date

2011-03-11

Citation:

APA:

Chappell, William H., & Steelman, Linda S., & Long, Jacquelyn M., & Kempf, Ruth C., & Abrams, Stephen L., & Franklin, Richard A., & Bäsecke, Jörg, & Stivala, Franca, & Donia, Marco, & Fagone, Paolo, & Malaponte, Graziella, & Mazzarino, Maria C., & Nicoletti, Ferdinando, & Libra, Massimo, & Maksimovic-Ivanic, Danijela, & Mijatovic, Sanja, & Montalto, Giuseppe, & Cervello, Melchiorre, & Laidler, Piotr, & Milella, Michele, & Tafuri, Agostino, & Bonati, Antonio, & Evangelisti, Camilla, & Cocco, Lucio, & Martelli, Alberto M., & McCubrey, James A.. (March 2011). Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health. Oncotarget, (2:3), p.135–164. Retrieved from http://hdl.handle.net/10342/7985

Display/Hide MLA, Chicago and APA citation formats.

MLA:

Chappell, William H., and Steelman, Linda S., and Long, Jacquelyn M., and Kempf, Ruth C., and Abrams, Stephen L., and Franklin, Richard A., and Bäsecke, Jörg, and Stivala, Franca, and Donia, Marco, and Fagone, Paolo, and Malaponte, Graziella, and Mazzarino, Maria C., and Nicoletti, Ferdinando, and Libra, Massimo, and Maksimovic-Ivanic, Danijela, and Mijatovic, Sanja, and Montalto, Giuseppe, and Cervello, Melchiorre, and Laidler, Piotr, and Milella, Michele, and Tafuri, Agostino, and Bonati, Antonio, and Evangelisti, Camilla, and Cocco, Lucio, and Martelli, Alberto M., and McCubrey, James A.. "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health". Oncotarget. 2:3. (135–164.), March 2011. December 09, 2022. http://hdl.handle.net/10342/7985.

Chicago:

Chappell, William H. and Steelman, Linda S. and Long, Jacquelyn M. and Kempf, Ruth C. and Abrams, Stephen L. and Franklin, Richard A. and Bäsecke, Jörg and Stivala, Franca and Donia, Marco and Fagone, Paolo and Malaponte, Graziella and Mazzarino, Maria C. and Nicoletti, Ferdinando and Libra, Massimo and Maksimovic-Ivanic, Danijela and Mijatovic, Sanja and Montalto, Giuseppe and Cervello, Melchiorre and Laidler, Piotr and Milella, Michele and Tafuri, Agostino and Bonati, Antonio and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M. and McCubrey, James A., "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health," Oncotarget 2, no. 3 (March 2011), http://hdl.handle.net/10342/7985 (accessed December 09, 2022).

AMA:

Chappell, William H., Steelman, Linda S., Long, Jacquelyn M., Kempf, Ruth C., Abrams, Stephen L., Franklin, Richard A., Bäsecke, Jörg, Stivala, Franca, Donia, Marco, Fagone, Paolo, Malaponte, Graziella, Mazzarino, Maria C., Nicoletti, Ferdinando, Libra, Massimo, Maksimovic-Ivanic, Danijela, Mijatovic, Sanja, Montalto, Giuseppe, Cervello, Melchiorre, Laidler, Piotr, Milella, Michele, Tafuri, Agostino, Bonati, Antonio, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M., McCubrey, James A.. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health. Oncotarget. March 2011; 2(3) 135–164. http://hdl.handle.net/10342/7985. Accessed December 09, 2022.

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