Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review)

Camilla Evangelisti, Cecilia Evangelisti, Francesca Chiarini, Annalisa Lonetti, Francesca Buontempo, Daniela Bressanin, Alessandra Cappellini, Ester Orsini, James A. McCubrey, Alberto M. Martelli

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15% of pediatric and 25% of adult ALL cases. Even if the prognosis of T-ALL has improved especially in the childhood due to the use of new intensified treatment protocols, the outcome of relapsed patients who are resistant to conventional chemotherapeutic drugs or who relapse is still poor. For this reason, there is a need for novel and less toxic targeted therapies against signaling pathways aberrantly activated in T-ALL, such as the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR). Small molecules designed to target key components of this signaling axis have proven their efficacy both in vitro and in vivo in pre-clinical settings of T-ALL. In particular, different classes of mTOR inhibitors have been disclosed by pharmaceutical companies, and they are currently being tested in clinical trials for treating T-ALL patients. One of the most promising approaches for the treatment of T-ALL seems to be the combination of mTOR inhibitors with traditional chemotherapeutic agents. This could lead to a lower drug dosage that may circumvent the systemic side effects of chemotherapeutics. In this review, we focus on the different classes of mTOR inhibitors that will possibly have an impact on the therapeutic arsenal we have at our disposal against T-ALL.

Original languageEnglish
Pages (from-to)909-918
Number of pages10
JournalInternational Journal of Oncology
Volume45
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Sirolimus
Therapeutics
Pharmaceutical Preparations
1-Phosphatidylinositol 4-Kinase
Poisons
Cell Lineage
Clinical Protocols
Clinical Trials
Pediatrics
T-Lymphocytes
Recurrence

Keywords

  • Leukemia initiating cells
  • Mammalian target of rapamycin
  • T-acute lymphoblastic leukemia
  • Targeted therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Evangelisti, C., Evangelisti, C., Chiarini, F., Lonetti, A., Buontempo, F., Bressanin, D., ... Martelli, A. M. (2014). Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review). International Journal of Oncology, 45(3), 909-918. https://doi.org/10.3892/ijo.2014.2525

Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review). / Evangelisti, Camilla; Evangelisti, Cecilia; Chiarini, Francesca; Lonetti, Annalisa; Buontempo, Francesca; Bressanin, Daniela; Cappellini, Alessandra; Orsini, Ester; McCubrey, James A.; Martelli, Alberto M.

In: International Journal of Oncology, Vol. 45, No. 3, 2014, p. 909-918.

Research output: Contribution to journalArticle

Evangelisti, C, Evangelisti, C, Chiarini, F, Lonetti, A, Buontempo, F, Bressanin, D, Cappellini, A, Orsini, E, McCubrey, JA & Martelli, AM 2014, 'Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review)', International Journal of Oncology, vol. 45, no. 3, pp. 909-918. https://doi.org/10.3892/ijo.2014.2525
Evangelisti C, Evangelisti C, Chiarini F, Lonetti A, Buontempo F, Bressanin D et al. Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review). International Journal of Oncology. 2014;45(3):909-918. https://doi.org/10.3892/ijo.2014.2525
Evangelisti, Camilla ; Evangelisti, Cecilia ; Chiarini, Francesca ; Lonetti, Annalisa ; Buontempo, Francesca ; Bressanin, Daniela ; Cappellini, Alessandra ; Orsini, Ester ; McCubrey, James A. ; Martelli, Alberto M. / Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review). In: International Journal of Oncology. 2014 ; Vol. 45, No. 3. pp. 909-918.
@article{3618124a64244de49ea75382de206173,
title = "Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review)",
abstract = "T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15{\%} of pediatric and 25{\%} of adult ALL cases. Even if the prognosis of T-ALL has improved especially in the childhood due to the use of new intensified treatment protocols, the outcome of relapsed patients who are resistant to conventional chemotherapeutic drugs or who relapse is still poor. For this reason, there is a need for novel and less toxic targeted therapies against signaling pathways aberrantly activated in T-ALL, such as the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR). Small molecules designed to target key components of this signaling axis have proven their efficacy both in vitro and in vivo in pre-clinical settings of T-ALL. In particular, different classes of mTOR inhibitors have been disclosed by pharmaceutical companies, and they are currently being tested in clinical trials for treating T-ALL patients. One of the most promising approaches for the treatment of T-ALL seems to be the combination of mTOR inhibitors with traditional chemotherapeutic agents. This could lead to a lower drug dosage that may circumvent the systemic side effects of chemotherapeutics. In this review, we focus on the different classes of mTOR inhibitors that will possibly have an impact on the therapeutic arsenal we have at our disposal against T-ALL.",
keywords = "Leukemia initiating cells, Mammalian target of rapamycin, T-acute lymphoblastic leukemia, Targeted therapy",
author = "Camilla Evangelisti and Cecilia Evangelisti and Francesca Chiarini and Annalisa Lonetti and Francesca Buontempo and Daniela Bressanin and Alessandra Cappellini and Ester Orsini and McCubrey, {James A.} and Martelli, {Alberto M.}",
year = "2014",
doi = "10.3892/ijo.2014.2525",
language = "English",
volume = "45",
pages = "909--918",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "3",

}

TY - JOUR

T1 - Therapeutic potential of targeting mTOR in T-cell acute lymphoblastic leukemia (Review)

AU - Evangelisti, Camilla

AU - Evangelisti, Cecilia

AU - Chiarini, Francesca

AU - Lonetti, Annalisa

AU - Buontempo, Francesca

AU - Bressanin, Daniela

AU - Cappellini, Alessandra

AU - Orsini, Ester

AU - McCubrey, James A.

AU - Martelli, Alberto M.

PY - 2014

Y1 - 2014

N2 - T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15% of pediatric and 25% of adult ALL cases. Even if the prognosis of T-ALL has improved especially in the childhood due to the use of new intensified treatment protocols, the outcome of relapsed patients who are resistant to conventional chemotherapeutic drugs or who relapse is still poor. For this reason, there is a need for novel and less toxic targeted therapies against signaling pathways aberrantly activated in T-ALL, such as the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR). Small molecules designed to target key components of this signaling axis have proven their efficacy both in vitro and in vivo in pre-clinical settings of T-ALL. In particular, different classes of mTOR inhibitors have been disclosed by pharmaceutical companies, and they are currently being tested in clinical trials for treating T-ALL patients. One of the most promising approaches for the treatment of T-ALL seems to be the combination of mTOR inhibitors with traditional chemotherapeutic agents. This could lead to a lower drug dosage that may circumvent the systemic side effects of chemotherapeutics. In this review, we focus on the different classes of mTOR inhibitors that will possibly have an impact on the therapeutic arsenal we have at our disposal against T-ALL.

AB - T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous neoplastic disorder of immature hematopoietic precursors committed to the T-cell lineage. T-ALL comprises about 15% of pediatric and 25% of adult ALL cases. Even if the prognosis of T-ALL has improved especially in the childhood due to the use of new intensified treatment protocols, the outcome of relapsed patients who are resistant to conventional chemotherapeutic drugs or who relapse is still poor. For this reason, there is a need for novel and less toxic targeted therapies against signaling pathways aberrantly activated in T-ALL, such as the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR). Small molecules designed to target key components of this signaling axis have proven their efficacy both in vitro and in vivo in pre-clinical settings of T-ALL. In particular, different classes of mTOR inhibitors have been disclosed by pharmaceutical companies, and they are currently being tested in clinical trials for treating T-ALL patients. One of the most promising approaches for the treatment of T-ALL seems to be the combination of mTOR inhibitors with traditional chemotherapeutic agents. This could lead to a lower drug dosage that may circumvent the systemic side effects of chemotherapeutics. In this review, we focus on the different classes of mTOR inhibitors that will possibly have an impact on the therapeutic arsenal we have at our disposal against T-ALL.

KW - Leukemia initiating cells

KW - Mammalian target of rapamycin

KW - T-acute lymphoblastic leukemia

KW - Targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=84904383690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904383690&partnerID=8YFLogxK

U2 - 10.3892/ijo.2014.2525

DO - 10.3892/ijo.2014.2525

M3 - Article

C2 - 24968804

AN - SCOPUS:84904383690

VL - 45

SP - 909

EP - 918

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 3

ER -