PMID- 27059645
OWN - NLM
STAT- MEDLINE
DCOM- 20171229
LR  - 20220310
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 82
IP  - 5
DP  - 2016 Nov
TI  - The therapeutic potential of mTOR inhibitors in breast cancer.
PG  - 1189-1212
LID - 10.1111/bcp.12958 [doi]
AB  - Rapamycin and modified rapamycins (rapalogs) have been used to prevent allograft 
      rejection after organ transplant for over 15 years. The mechanistic target of 
      rapamycin (mTOR) has been determined to be a key component of the mTORC1 complex 
      which consists of the serine/threonine kinase TOR and at least five other 
      proteins which are involved in regulating its activity. Some of the best 
      characterized substrates of mTORC1 are proteins which are key kinases involved in 
      the regulation of cell growth (e.g., p70S6K) and protein translation (e.g., 
      4E-BP1). These proteins may in some cases serve as indicators to sensitivity to 
      rapamycin-related therapies. Dysregulation of mTORC1 activity frequently occurs 
      due to mutations at, or amplifications of, upstream growth factor receptors 
      (e.g., human epidermal growth factor receptor-2, HER2) as well as kinases (e.g., 
      PI3K) and phosphatases (e.g., PTEN) critical in the regulation of cell growth. 
      More recently, it has been shown that certain rapalogs may enhance the 
      effectiveness of hormonal-based therapies for breast cancer patients who have 
      become resistant to endocrine therapy. The combined treatment of certain rapalogs 
      (e.g., everolimus) and aromatase inhibitors (e.g., exemestane) has been approved 
      by the United States Food and Drug Administration (US FDA) and other drug 
      regulatory agencies to treat estrogen receptor positive (ER+) breast cancer 
      patients who have become resistant to hormonal-based therapies and have 
      progressed. This review will summarize recent basic and clinical research in the 
      area and evaluate potential novel therapeutic approaches.
CI  - (c) 2016 The British Pharmacological Society.
FAU - Steelman, Linda S
AU  - Steelman LS
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA.
FAU - Martelli, Alberto M
AU  - Martelli AM
AD  - Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, 
      Bologna, Italy.
FAU - Cocco, Lucio
AU  - Cocco L
AD  - Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, 
      Bologna, Italy.
FAU - Libra, Massimo
AU  - Libra M
AD  - Department of Biomedical and Biotechnological Sciences, Laboratory of 
      Translational Oncology & Functional Genomics, Section of Pathology & Oncology, 
      University of Catania, Catania, Italy.
FAU - Nicoletti, Ferdinando
AU  - Nicoletti F
AD  - Department of Biomedical and Biotechnological Sciences, Laboratory of 
      Translational Oncology & Functional Genomics, Section of Pathology & Oncology, 
      University of Catania, Catania, Italy.
FAU - Abrams, Stephen L
AU  - Abrams SL
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA.
FAU - McCubrey, James A
AU  - McCubrey JA
AD  - Department of Microbiology and Immunology, Brody School of Medicine at East 
      Carolina University, Greenville, NC, USA. mccubreyj@ecu.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160510
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Aromatase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Aromatase Inhibitors/therapeutic use
MH  - Breast Neoplasms/*drug therapy
MH  - Female
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1/*antagonists & inhibitors
MH  - Models, Biological
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Signal Transduction/drug effects
PMC - PMC5061784
OTO - NOTNLM
OT  - drug resistance
OT  - endocrine resistance
OT  - everolimus
OT  - exemestane
OT  - metastasis
OT  - rapamycin
EDAT- 2016/04/10 06:00
MHDA- 2017/12/30 06:00
PMCR- 2017/11/01
CRDT- 2016/04/10 06:00
PHST- 2015/12/16 00:00 [received]
PHST- 2016/03/29 00:00 [revised]
PHST- 2016/03/31 00:00 [accepted]
PHST- 2016/04/10 06:00 [pubmed]
PHST- 2017/12/30 06:00 [medline]
PHST- 2016/04/10 06:00 [entrez]
PHST- 2017/11/01 00:00 [pmc-release]
AID - BCP12958 [pii]
AID - 10.1111/bcp.12958 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 Nov;82(5):1189-1212. doi: 10.1111/bcp.12958. Epub 2016 
      May 10.