mTOR pathway and mTOR inhibitors as agents for cancer therapy

Paolo Baldo, Sara Cecco, Elisa Giacomin, Renzo Lazzarini, Barbara Ros, Stefano Marastoni

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Research into mTOR, mammalian Target Of Rapamycin as an important drug target continues to be extremely interesting, both in terms of the increased molecular knowledge being acquired at the basis of various human diseases, and also for possible applications in drug cancer therapy. The mTOR signaling system plays a key role in several transduction pathways that are necessary for cell cycle progression and cellular proliferation. Drugs known as mTOR inhibitors have been included in ongoing and in recently completed cancer trials. New insights into the mTOR signaling system are helping to clarify the functionality of key mTOR components, and especially their possible role in apoptosis, angiogenesis and tumor progression. Three other molecules, already approved for therapeutic use and being commercialized (Everolimius, Temsirolimus and Zotarolimus) are added to Rapamycin (also known as Sirolimus), the parent drug of the mTOR inhibitors. Of these, only Temsirolimus is currently approved in the treatment of renal cell carcinoma, while the others are approved for organ transplant rejection and coronary artery restenosis. There are at least 10 other molecules currently under development for clinical and preclinical studies. This review offers an updated synopsis of the mTOR signaling system, in particular as regards relevant aspects of cancer research, looks at the known mTOR inhibitors and gives a systematic vision of current trials for each individual molecule subject to clinical investigation.

Original languageEnglish
Pages (from-to)647-665
Number of pages19
JournalCurrent Cancer Drug Targets
Volume8
Issue number8
DOIs
Publication statusPublished - Dec 2008

Fingerprint

Sirolimus
Neoplasms
Pharmaceutical Preparations
Coronary Restenosis
Graft Rejection
Therapeutic Uses
Therapeutics
Renal Cell Carcinoma
Research
Coronary Vessels
Cell Cycle
Cell Proliferation
Apoptosis
Transplants
Drug Therapy
temsirolimus

Keywords

  • Cancer therapy
  • Clinical trial
  • Drug discovery
  • Investigational drugs
  • Molecular target
  • mTOR
  • Pathway
  • Rapamycin
  • Signal-tranduction

ASJC Scopus subject areas

  • Cancer Research
  • Drug Discovery
  • Pharmacology

Cite this

Baldo, P., Cecco, S., Giacomin, E., Lazzarini, R., Ros, B., & Marastoni, S. (2008). mTOR pathway and mTOR inhibitors as agents for cancer therapy. Current Cancer Drug Targets, 8(8), 647-665. https://doi.org/10.2174/156800908786733513

mTOR pathway and mTOR inhibitors as agents for cancer therapy. / Baldo, Paolo; Cecco, Sara; Giacomin, Elisa; Lazzarini, Renzo; Ros, Barbara; Marastoni, Stefano.

In: Current Cancer Drug Targets, Vol. 8, No. 8, 12.2008, p. 647-665.

Research output: Contribution to journalArticle

Baldo, P, Cecco, S, Giacomin, E, Lazzarini, R, Ros, B & Marastoni, S 2008, 'mTOR pathway and mTOR inhibitors as agents for cancer therapy', Current Cancer Drug Targets, vol. 8, no. 8, pp. 647-665. https://doi.org/10.2174/156800908786733513
Baldo, Paolo ; Cecco, Sara ; Giacomin, Elisa ; Lazzarini, Renzo ; Ros, Barbara ; Marastoni, Stefano. / mTOR pathway and mTOR inhibitors as agents for cancer therapy. In: Current Cancer Drug Targets. 2008 ; Vol. 8, No. 8. pp. 647-665.
@article{a4510a8403c84974899c86d02b9246c0,
title = "mTOR pathway and mTOR inhibitors as agents for cancer therapy",
abstract = "Research into mTOR, mammalian Target Of Rapamycin as an important drug target continues to be extremely interesting, both in terms of the increased molecular knowledge being acquired at the basis of various human diseases, and also for possible applications in drug cancer therapy. The mTOR signaling system plays a key role in several transduction pathways that are necessary for cell cycle progression and cellular proliferation. Drugs known as mTOR inhibitors have been included in ongoing and in recently completed cancer trials. New insights into the mTOR signaling system are helping to clarify the functionality of key mTOR components, and especially their possible role in apoptosis, angiogenesis and tumor progression. Three other molecules, already approved for therapeutic use and being commercialized (Everolimius, Temsirolimus and Zotarolimus) are added to Rapamycin (also known as Sirolimus), the parent drug of the mTOR inhibitors. Of these, only Temsirolimus is currently approved in the treatment of renal cell carcinoma, while the others are approved for organ transplant rejection and coronary artery restenosis. There are at least 10 other molecules currently under development for clinical and preclinical studies. This review offers an updated synopsis of the mTOR signaling system, in particular as regards relevant aspects of cancer research, looks at the known mTOR inhibitors and gives a systematic vision of current trials for each individual molecule subject to clinical investigation.",
keywords = "Cancer therapy, Clinical trial, Drug discovery, Investigational drugs, Molecular target, mTOR, Pathway, Rapamycin, Signal-tranduction",
author = "Paolo Baldo and Sara Cecco and Elisa Giacomin and Renzo Lazzarini and Barbara Ros and Stefano Marastoni",
year = "2008",
month = "12",
doi = "10.2174/156800908786733513",
language = "English",
volume = "8",
pages = "647--665",
journal = "Current Cancer Drug Targets",
issn = "1568-0096",
publisher = "Bentham Science Publishers B.V.",
number = "8",

}

TY - JOUR

T1 - mTOR pathway and mTOR inhibitors as agents for cancer therapy

AU - Baldo, Paolo

AU - Cecco, Sara

AU - Giacomin, Elisa

AU - Lazzarini, Renzo

AU - Ros, Barbara

AU - Marastoni, Stefano

PY - 2008/12

Y1 - 2008/12

N2 - Research into mTOR, mammalian Target Of Rapamycin as an important drug target continues to be extremely interesting, both in terms of the increased molecular knowledge being acquired at the basis of various human diseases, and also for possible applications in drug cancer therapy. The mTOR signaling system plays a key role in several transduction pathways that are necessary for cell cycle progression and cellular proliferation. Drugs known as mTOR inhibitors have been included in ongoing and in recently completed cancer trials. New insights into the mTOR signaling system are helping to clarify the functionality of key mTOR components, and especially their possible role in apoptosis, angiogenesis and tumor progression. Three other molecules, already approved for therapeutic use and being commercialized (Everolimius, Temsirolimus and Zotarolimus) are added to Rapamycin (also known as Sirolimus), the parent drug of the mTOR inhibitors. Of these, only Temsirolimus is currently approved in the treatment of renal cell carcinoma, while the others are approved for organ transplant rejection and coronary artery restenosis. There are at least 10 other molecules currently under development for clinical and preclinical studies. This review offers an updated synopsis of the mTOR signaling system, in particular as regards relevant aspects of cancer research, looks at the known mTOR inhibitors and gives a systematic vision of current trials for each individual molecule subject to clinical investigation.

AB - Research into mTOR, mammalian Target Of Rapamycin as an important drug target continues to be extremely interesting, both in terms of the increased molecular knowledge being acquired at the basis of various human diseases, and also for possible applications in drug cancer therapy. The mTOR signaling system plays a key role in several transduction pathways that are necessary for cell cycle progression and cellular proliferation. Drugs known as mTOR inhibitors have been included in ongoing and in recently completed cancer trials. New insights into the mTOR signaling system are helping to clarify the functionality of key mTOR components, and especially their possible role in apoptosis, angiogenesis and tumor progression. Three other molecules, already approved for therapeutic use and being commercialized (Everolimius, Temsirolimus and Zotarolimus) are added to Rapamycin (also known as Sirolimus), the parent drug of the mTOR inhibitors. Of these, only Temsirolimus is currently approved in the treatment of renal cell carcinoma, while the others are approved for organ transplant rejection and coronary artery restenosis. There are at least 10 other molecules currently under development for clinical and preclinical studies. This review offers an updated synopsis of the mTOR signaling system, in particular as regards relevant aspects of cancer research, looks at the known mTOR inhibitors and gives a systematic vision of current trials for each individual molecule subject to clinical investigation.

KW - Cancer therapy

KW - Clinical trial

KW - Drug discovery

KW - Investigational drugs

KW - Molecular target

KW - mTOR

KW - Pathway

KW - Rapamycin

KW - Signal-tranduction

UR - http://www.scopus.com/inward/record.url?scp=57449111076&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57449111076&partnerID=8YFLogxK

U2 - 10.2174/156800908786733513

DO - 10.2174/156800908786733513

M3 - Article

VL - 8

SP - 647

EP - 665

JO - Current Cancer Drug Targets

JF - Current Cancer Drug Targets

SN - 1568-0096

IS - 8

ER -