TY  - JOUR
AU  - McCubrey, James A
AU  - Steelman, Linda S
AU  - Abrams, Stephen L
AU  - Misaghian, Negin
AU  - Chappell, William H
AU  - Baesecke, Joerg
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Ligresti, Giovanni
AU  - Stivala, Franca
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - Laidler, Piotr
AU  - Bonati, Antonio
AU  - Evangelisti, Camilla
AU  - Cocco, Lucio
AU  - Martelli, Alberto M
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1183
AB  - An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models.
T2  - Current Pharmaceutical Design
T1  - Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy
IS  - 13
VL  - 18
EP  - 1795
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1183
ER  - 

@article{
author = "McCubrey, James A and Steelman, Linda S and Abrams, Stephen L and Misaghian, Negin and Chappell, William H and Baesecke, Joerg and Nicoletti, Ferdinando and Libra, Massimo and Ligresti, Giovanni and Stivala, Franca and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Montalto, Giuseppe and Cervello, Melchiorre and Laidler, Piotr and Bonati, Antonio and Evangelisti, Camilla and Cocco, Lucio and Martelli, Alberto M",
year = "2012",
abstract = "An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the original therapeutic approach or they have acquired mutations which confer resistance to the primary therapy. In experimental mouse tumor transplant models, CICs have the ability to transfer the tumor to immunocompromised mice very efficiently while the BCs are not able to do so as effectively. Often CICs display increased expression of proteins involved in drug resistance and hence they are intrinsically resistant to many chemotherapeutic approaches. Furthermore, the CICs may be in a suspended state of proliferation and not sensitive to common chemotherapeutic and radiological approaches often employed to eliminate the rapidly proliferating BCs. Promising therapeutic approaches include the targeting of certain signal transduction pathways (e.g., RAC, WNT, PI3K, PML) with small molecule inhibitors or targeting specific cell-surface molecules (e.g., CD44), with effective cytotoxic antibodies. The existence of CICs could explain the high frequency of relapse and resistance to many currently used cancer therapies. New approaches should be developed to effectively target the CIC which could vastly improve cancer therapies and outcomes. This review will discuss recent concepts of targeting CICs in certain leukemia models.",
journal = "Current Pharmaceutical Design",
title = "Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy",
number = "13",
volume = "18",
pages = "1795",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1183"
}

McCubrey, J. A., Steelman, L. S., Abrams, S. L., Misaghian, N., Chappell, W. H., Baesecke, J., Nicoletti, F., Libra, M., Ligresti, G., Stivala, F., Maksimović-Ivanić, D., Mijatović, S., Montalto, G., Cervello, M., Laidler, P., Bonati, A., Evangelisti, C., Cocco, L.,& Martelli, A. M.. (2012). Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy. in Current Pharmaceutical Design, 18(13).
https://hdl.handle.net/21.15107/rcub_ibiss_1183

McCubrey JA, Steelman LS, Abrams SL, Misaghian N, Chappell WH, Baesecke J, Nicoletti F, Libra M, Ligresti G, Stivala F, Maksimović-Ivanić D, Mijatović S, Montalto G, Cervello M, Laidler P, Bonati A, Evangelisti C, Cocco L, Martelli AM. Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy. in Current Pharmaceutical Design. 2012;18(13):null-1795.
https://hdl.handle.net/21.15107/rcub_ibiss_1183 .

McCubrey, James A, Steelman, Linda S, Abrams, Stephen L, Misaghian, Negin, Chappell, William H, Baesecke, Joerg, Nicoletti, Ferdinando, Libra, Massimo, Ligresti, Giovanni, Stivala, Franca, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Montalto, Giuseppe, Cervello, Melchiorre, Laidler, Piotr, Bonati, Antonio, Evangelisti, Camilla, Cocco, Lucio, Martelli, Alberto M, "Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy" in Current Pharmaceutical Design, 18, no. 13 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1183 .

TY  - JOUR
AU  - Steelman, Linda S
AU  - Chappell, William H
AU  - Abrams, Stephen L
AU  - Kempf, C Ruth
AU  - Long, Jacquelyn M
AU  - Laidler, Piotr
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Stivala, Franca
AU  - Mazzarino, Maria C
AU  - Donia, Marco
AU  - Fagone, Paolo
AU  - Malaponte, Graziella
AU  - Nicoletti, Ferdinando
AU  - Libra, Massimo
AU  - Milella, Michele
AU  - Tafuri, Agostino
AU  - Bonati, Antonio
AU  - Baesecke, Joerg
AU  - Cocco, Lucio
AU  - Evangelisti, Camilla
AU  - Martelli, Alberto M
AU  - Montalto, Giuseppe
AU  - Cervello, Melchiorre
AU  - McCubrey, James A
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1302
UR  - https://www.aging-us.com/article/100296
AB  - Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.
T2  - Aging-US
T1  - Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging
IS  - 3
VL  - 3
DO  - 10.18632/aging.100296
EP  - 222
ER  - 

@article{
author = "Steelman, Linda S and Chappell, William H and Abrams, Stephen L and Kempf, C Ruth and Long, Jacquelyn M and Laidler, Piotr and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Stivala, Franca and Mazzarino, Maria C and Donia, Marco and Fagone, Paolo and Malaponte, Graziella and Nicoletti, Ferdinando and Libra, Massimo and Milella, Michele and Tafuri, Agostino and Bonati, Antonio and Baesecke, Joerg and Cocco, Lucio and Evangelisti, Camilla and Martelli, Alberto M and Montalto, Giuseppe and Cervello, Melchiorre and McCubrey, James A",
year = "2011",
abstract = "Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.",
journal = "Aging-US",
title = "Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging",
number = "3",
volume = "3",
doi = "10.18632/aging.100296",
pages = "222"
}

Steelman, L. S., Chappell, W. H., Abrams, S. L., Kempf, C. R., Long, J. M., Laidler, P., Mijatović, S., Maksimović-Ivanić, D., Stivala, F., Mazzarino, M. C., Donia, M., Fagone, P., Malaponte, G., Nicoletti, F., Libra, M., Milella, M., Tafuri, A., Bonati, A., Baesecke, J., Cocco, L., Evangelisti, C., Martelli, A. M., Montalto, G., Cervello, M.,& McCubrey, J. A.. (2011). Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. in Aging-US, 3(3).
https://doi.org/10.18632/aging.100296

Steelman LS, Chappell WH, Abrams SL, Kempf CR, Long JM, Laidler P, Mijatović S, Maksimović-Ivanić D, Stivala F, Mazzarino MC, Donia M, Fagone P, Malaponte G, Nicoletti F, Libra M, Milella M, Tafuri A, Bonati A, Baesecke J, Cocco L, Evangelisti C, Martelli AM, Montalto G, Cervello M, McCubrey JA. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. in Aging-US. 2011;3(3):null-222.
doi:10.18632/aging.100296 .

Steelman, Linda S, Chappell, William H, Abrams, Stephen L, Kempf, C Ruth, Long, Jacquelyn M, Laidler, Piotr, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Stivala, Franca, Mazzarino, Maria C, Donia, Marco, Fagone, Paolo, Malaponte, Graziella, Nicoletti, Ferdinando, Libra, Massimo, Milella, Michele, Tafuri, Agostino, Bonati, Antonio, Baesecke, Joerg, Cocco, Lucio, Evangelisti, Camilla, Martelli, Alberto M, Montalto, Giuseppe, Cervello, Melchiorre, McCubrey, James A, "Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging" in Aging-US, 3, no. 3 (2011),
https://doi.org/10.18632/aging.100296 . .

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 . .