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  - 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 .

TY  - JOUR
AU  - Chappell, William H
AU  - Steelman, Linda S
AU  - Long, Jacquelyn M
AU  - Kempf, Ruth C
AU  - Abrams, Stephen L
AU  - Franklin, Richard A
AU  - Baesecke, Joerg
AU  - Stivala, Franca
AU  - Donia, Marco
AU  - Fagone, Paolo
AU  - Malaponte, Graziella
AU  - Mazzarino, Maria C
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Laidler, Piotr
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Bonati, Antonio
AU  - Evangelisti, Camilla
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
AU  - McCubrey, James A
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1300
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). 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.
T2  - Oncotarget
T1  - Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health
IS  - 3
VL  - 2
DO  - 10.18632/oncotarget.240
EP  - 164
ER  - 

@article{
author = "Chappell, William H and Steelman, Linda S and Long, Jacquelyn M and Kempf, Ruth C and Abrams, Stephen L and Franklin, Richard A and Baesecke, Joerg and Stivala, Franca and Donia, Marco and Fagone, Paolo and Malaponte, Graziella and Mazzarino, Maria C and Nicoletti, Ferdinando and Libra, Massimo and Maksimović-Ivanić, Danijela and Mijatović, 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",
year = "2011",
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.",
journal = "Oncotarget",
title = "Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health",
number = "3",
volume = "2",
doi = "10.18632/oncotarget.240",
pages = "164"
}

Chappell, W. H., Steelman, L. S., Long, J. M., Kempf, R. C., Abrams, S. L., Franklin, R. A., Baesecke, J., Stivala, F., Donia, M., Fagone, P., Malaponte, G., Mazzarino, M. C., Nicoletti, F., Libra, M., Maksimović-Ivanić, D., Mijatović, S., Montalto, G., Cervello, M., Laidler, P., Milella, M., Tafuri, A., Bonati, A., Evangelisti, C., Cocco, L., Martelli, A. M.,& McCubrey, J. A.. (2011). Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health. in Oncotarget, 2(3).
https://doi.org/10.18632/oncotarget.240

Chappell WH, Steelman LS, Long JM, Kempf RC, Abrams SL, Franklin RA, Baesecke J, Stivala F, Donia M, Fagone P, Malaponte G, Mazzarino MC, Nicoletti F, Libra M, Maksimović-Ivanić D, Mijatović S, Montalto G, Cervello M, Laidler P, Milella M, Tafuri A, Bonati A, Evangelisti C, Cocco L, Martelli AM, McCubrey JA. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health. in Oncotarget. 2011;2(3):null-164.
doi:10.18632/oncotarget.240 .

Chappell, William H, Steelman, Linda S, Long, Jacquelyn M, Kempf, Ruth C, Abrams, Stephen L, Franklin, Richard A, Baesecke, Joerg, Stivala, Franca, Donia, Marco, Fagone, Paolo, Malaponte, Graziella, Mazzarino, Maria C, Nicoletti, Ferdinando, Libra, Massimo, Maksimović-Ivanić, Danijela, Mijatović, 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" in Oncotarget, 2, no. 3 (2011),
https://doi.org/10.18632/oncotarget.240 . .