TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Franklin, Richard A
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Fagone, Paolo
AU  - Nicoletti, Ferdinando
AU  - Baesecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Chiarini, Francesca
AU  - Evangelisti, Camilla
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1096
AB  - 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.
T2  - Oncotarget
T1  - Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance
IS  - 10
VL  - 3
DO  - 10.18632/oncotarget.659
SP  - 389
EP  - 1111
ER  - 

@article{
author = "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 Baesecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Milella, Michele and Tafuri, Agostino and Chiarini, Francesca and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M",
year = "2012",
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.",
journal = "Oncotarget",
title = "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance",
number = "10",
volume = "3",
doi = "10.18632/oncotarget.659",
pages = "389-1111"
}

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Franklin, R. A., Montalto, G., Cervello, M., Libra, M., Candido, S., Malaponte, G., Mazzarino, M. C., Fagone, P., Nicoletti, F., Baesecke, J., Mijatović, S., Maksimović-Ivanić, D., Milella, M., Tafuri, A., Chiarini, F., Evangelisti, C., Cocco, L.,& Martelli, A. M.. (2012). Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance. in Oncotarget, 3(10), 389-1111.
https://doi.org/10.18632/oncotarget.659

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Franklin RA, Montalto G, Cervello M, Libra M, Candido S, Malaponte G, Mazzarino MC, Fagone P, Nicoletti F, Baesecke J, Mijatović S, Maksimović-Ivanić D, Milella M, Tafuri A, Chiarini F, Evangelisti C, Cocco L, Martelli AM. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance. in Oncotarget. 2012;3(10):389-1111.
doi:10.18632/oncotarget.659 .

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, Baesecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, 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" in Oncotarget, 3, no. 10 (2012):389-1111,
https://doi.org/10.18632/oncotarget.659 . .

TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Nicoletti, Ferdinando
AU  - Fagone, Paolo
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Candido, Saverio
AU  - Libra, Massimo
AU  - Baesecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Cocco, Lucio
AU  - Evangelisti, Camilla
AU  - Chiarini, Francesca
AU  - Martelli, Alberto M
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1109
AB  - 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.
T2  - Oncotarget
T1  - Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.
IS  - 9
VL  - 3
DO  - 10.18632/oncotarget.652
SP  - 153
EP  - 987
ER  - 

@article{
author = "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, Graziella and Mazzarino, Maria C and Candido, Saverio and Libra, Massimo and Baesecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Milella, Michele and Tafuri, Agostino and Cocco, Lucio and Evangelisti, Camilla and Chiarini, Francesca and Martelli, Alberto M",
year = "2012",
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). 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.",
journal = "Oncotarget",
title = "Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.",
number = "9",
volume = "3",
doi = "10.18632/oncotarget.652",
pages = "153-987"
}

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Abrams, S. L., Montalto, G., Cervello, M., Nicoletti, F., Fagone, P., Malaponte, G., Mazzarino, M. C., Candido, S., Libra, M., Baesecke, J., Mijatović, S., Maksimović-Ivanić, D., Milella, M., Tafuri, A., Cocco, L., Evangelisti, C., Chiarini, F.,& Martelli, A. M.. (2012). Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.. in Oncotarget, 3(9), 153-987.
https://doi.org/10.18632/oncotarget.652

McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Montalto G, Cervello M, Nicoletti F, Fagone P, Malaponte G, Mazzarino MC, Candido S, Libra M, Baesecke J, Mijatović S, Maksimović-Ivanić D, Milella M, Tafuri A, Cocco L, Evangelisti C, Chiarini F, Martelli AM. Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.. in Oncotarget. 2012;3(9):153-987.
doi:10.18632/oncotarget.652 .

McCubrey, James A, Steelman, Linda S, Chappell, William H, Abrams, Stephen L, Montalto, Giuseppe, Cervello, Melchiorre, Nicoletti, Ferdinando, Fagone, Paolo, Malaponte, Graziella, Mazzarino, Maria C, Candido, Saverio, Libra, Massimo, Baesecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, 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." in Oncotarget, 3, no. 9 (2012):153-987,
https://doi.org/10.18632/oncotarget.652 . .

TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Sun, Lin
AU  - Davis, Nicole M
AU  - Abrams, Stephen L
AU  - Franklin, Richard A
AU  - Cocco, Lucio
AU  - Evangelisti, Camilla
AU  - Chiarini, Francesca
AU  - Martelli, Alberto M
AU  - Libra, Massimo
AU  - Candido, Saverio
AU  - Ligresti, Giovanni
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Fagone, Paolo
AU  - Donia, Marco
AU  - Nicoletti, Ferdinando
AU  - Polesel, Jerry
AU  - Talamini, Renato
AU  - Baesecke, Joerg
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Dulinska-Litewka, Joanna
AU  - Laidler, Piotr
AU  - D'Assoro, Antonio B
AU  - Drobot, Lyudmyla
AU  - Umezawa, Kazuo
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Demidenko, Zoya N
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1071
AB  - Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies.
T2  - Oncotarget
T1  - Advances in Targeting Signal Transduction Pathways
IS  - 12
VL  - 3
SP  - 69
EP  - 1521
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1071
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Chappell, William H and Sun, Lin and Davis, Nicole M and Abrams, Stephen L and Franklin, Richard A and Cocco, Lucio and Evangelisti, Camilla and Chiarini, Francesca and Martelli, Alberto M and Libra, Massimo and Candido, Saverio and Ligresti, Giovanni and Malaponte, Graziella and Mazzarino, Maria C and Fagone, Paolo and Donia, Marco and Nicoletti, Ferdinando and Polesel, Jerry and Talamini, Renato and Baesecke, Joerg and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Milella, Michele and Tafuri, Agostino and Dulinska-Litewka, Joanna and Laidler, Piotr and D'Assoro, Antonio B and Drobot, Lyudmyla and Umezawa, Kazuo and Montalto, Giuseppe and Cervello, Melchiorre and Demidenko, Zoya N",
year = "2012",
abstract = "Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies.",
journal = "Oncotarget",
title = "Advances in Targeting Signal Transduction Pathways",
number = "12",
volume = "3",
pages = "69-1521",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1071"
}

McCubrey, J. A., Steelman, L. S., Chappell, W. H., Sun, L., Davis, N. M., Abrams, S. L., Franklin, R. A., Cocco, L., Evangelisti, C., Chiarini, F., Martelli, A. M., Libra, M., Candido, S., Ligresti, G., Malaponte, G., Mazzarino, M. C., Fagone, P., Donia, M., Nicoletti, F., Polesel, J., Talamini, R., Baesecke, J., Mijatović, S., Maksimović-Ivanić, D., Milella, M., Tafuri, A., Dulinska-Litewka, J., Laidler, P., D'Assoro, A. B., Drobot, L., Umezawa, K., Montalto, G., Cervello, M.,& Demidenko, Z. N.. (2012). Advances in Targeting Signal Transduction Pathways. in Oncotarget, 3(12), 69-1521.
https://hdl.handle.net/21.15107/rcub_ibiss_1071

McCubrey JA, Steelman LS, Chappell WH, Sun L, Davis NM, Abrams SL, Franklin RA, Cocco L, Evangelisti C, Chiarini F, Martelli AM, Libra M, Candido S, Ligresti G, Malaponte G, Mazzarino MC, Fagone P, Donia M, Nicoletti F, Polesel J, Talamini R, Baesecke J, Mijatović S, Maksimović-Ivanić D, Milella M, Tafuri A, Dulinska-Litewka J, Laidler P, D'Assoro AB, Drobot L, Umezawa K, Montalto G, Cervello M, Demidenko ZN. Advances in Targeting Signal Transduction Pathways. in Oncotarget. 2012;3(12):69-1521.
https://hdl.handle.net/21.15107/rcub_ibiss_1071 .

McCubrey, James A, Steelman, Linda S, Chappell, William H, Sun, Lin, Davis, Nicole M, Abrams, Stephen L, Franklin, Richard A, Cocco, Lucio, Evangelisti, Camilla, Chiarini, Francesca, Martelli, Alberto M, Libra, Massimo, Candido, Saverio, Ligresti, Giovanni, Malaponte, Graziella, Mazzarino, Maria C, Fagone, Paolo, Donia, Marco, Nicoletti, Ferdinando, Polesel, Jerry, Talamini, Renato, Baesecke, Joerg, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Milella, Michele, Tafuri, Agostino, Dulinska-Litewka, Joanna, Laidler, Piotr, D'Assoro, Antonio B, Drobot, Lyudmyla, Umezawa, Kazuo, Montalto, Giuseppe, Cervello, Melchiorre, Demidenko, Zoya N, "Advances in Targeting Signal Transduction Pathways" in Oncotarget, 3, no. 12 (2012):69-1521,
https://hdl.handle.net/21.15107/rcub_ibiss_1071 .