PMID- 22475451
OWN - NLM
STAT- MEDLINE
DCOM- 20120906
LR  - 20211203
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 18
IP  - 19
DP  - 2012
TI  - Targeting mTOR pathways in human malignancies.
PG  - 2766-77
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is a protein kinase involved 
      in the phosphatidylinositol 3-Kinase (PI3K)/AKT signalling pathway with a central 
      role in the control of cell growth, survival and angiogenesis. Multiple and 
      frequent dysregulations of this pathway in human tumors make it a central target 
      in the development of new anticancer treatments. OBJECTIVE: To review the most 
      significant data on mTOR pathway, role of mTOR inhibitors in cancer treatment, 
      preclinical and clinical data of the three first generation mTOR inhibitors 
      (temsirolimus, everolimus and deferolimus), rationales, preclinical and clinical 
      data of second generation mTOR inhibitors. METHODS: Review of published 
      literature on mTOR and related pathways, rapalogs and novel mTOR inhibitors. 
      RESULTS/CONCLUSIONS: Temsirolimus and everolimus have been approved for the 
      treatment of metastatic Renal Cell Carcinoma (RCC), temsirolimus also for Mantle 
      Cell Lymphoma (MCL) and everolimus will be approved for pancreatic neuroendocrine 
      tumors; all three rapalogs are currently evaluated in phase III studies in 
      several tumors. Only limited published data are available on new mTOR inhibitors; 
      however, in vitro and in vivo in preclinical studies they have shown a 
      significant antiproliferative activity against a broad panel of tumors and a 
      favourable safety profile, with disease stabilization or even tumor regression, 
      either as single agent or in combination.
FAU - Fasolo, Angelica
AU  - Fasolo A
AD  - Unit of New Drugs & Innovative Therapies, Department of Medical Oncology 
      Fondazione Centro San Raffaele del Monte Tabor, Via Olgettina n degrees  60, 20132, 
      Milano, Italy. fasolo.angelica@hsr.it
FAU - Sessa, Cristiana
AU  - Sessa C
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 624KN6GM2T (temsirolimus)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Everolimus
MH  - Humans
MH  - Neoplasms/drug therapy/*physiopathology
MH  - Signal Transduction
MH  - Sirolimus/analogs & derivatives/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism/*physiology
EDAT- 2012/04/06 06:00
MHDA- 2012/09/07 06:00
CRDT- 2012/04/06 06:00
PHST- 2011/11/22 00:00 [received]
PHST- 2012/02/22 00:00 [accepted]
PHST- 2012/04/06 06:00 [entrez]
PHST- 2012/04/06 06:00 [pubmed]
PHST- 2012/09/07 06:00 [medline]
AID - CPD-EPUB-20120405-003 [pii]
AID - 10.2174/138161212800626210 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2012;18(19):2766-77. doi: 10.2174/138161212800626210.