Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: How mutations can result in therapy resistance and how to overcome resistance
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, Grazia; 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). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.
Date
2012-10-20
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, Grazia, & 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.
,
(),
-
. Retrieved from
http://hdl.handle.net/10342/7913
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, Grazia, 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". .
. (),
October 2012.
December 04, 2023.
http://hdl.handle.net/10342/7913.
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, Grazia 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," , no.
(October 2012),
http://hdl.handle.net/10342/7913 (accessed
December 04, 2023).
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, Grazia, 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. .
October 2012;
():
.
http://hdl.handle.net/10342/7913. Accessed
December 04, 2023.
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