PMID- 21116000
OWN - NLM
STAT- MEDLINE
DCOM- 20110314
LR  - 20211203
IS  - 1535-2900 (Electronic)
IS  - 1079-2082 (Linking)
VI  - 67
IP  - 24
DP  - 2010 Dec 15
TI  - Mammalian target of rapamycin: biological function and target for novel 
      anticancer agents.
PG  - 2095-106
LID - 10.2146/ajhp100020 [doi]
AB  - PURPOSE: The biological function of the mammalian target of rapamycin (mTOR) and 
      mechanisms of action of mTOR inhibitors currently available for clinical use are 
      described. SUMMARY: mTOR is a target for anticancer agents due to its role in 
      cancer development, progression, and resistance to other antineoplastic agents. 
      Currently, two mTOR inhibitors, temsirolimus and everolimus, are approved for the 
      treatment of patients with advanced renal cell carcinoma (RCC). Clinical trials 
      comparing single-agent temsirolimus with interferon alfa-2a demonstrated an 
      improvement in overall survival and progression-free survival (PFS) in patients 
      with metastatic RCC. Clinical studies comparing everolimus with placebo indicated 
      improved PFS in advanced RCC patients whose disease had progressed on or after 
      vascular endothelial growth factor (VEGF) inhibitor therapy. Due to its role in 
      the phosphatidylinositol 3-kinase (PI3K) signaling pathway, mTOR is a rational 
      target for inhibition in combination with other agents, including traditional 
      chemotherapy and agents that are affected by or target the PI3K pathway. Data 
      from these studies review the use of mTOR inhibitors in non-Hodgkin's lymphoma 
      and endometrial, breast, and neuroendocrine tumors. Common toxicities of mTOR 
      inhibitors include mucositis, stomatitis, rash, asthenia, fatigue, and 
      myelosuppression. Additional toxicities requiring monitoring include 
      hyperglycemia, hyperlipidemia, and pneumonitis. CONCLUSION: The mTOR signaling 
      pathway is upregulated in a variety of solid and hematologic tumors. Two 
      inhibitors of this pathway, temsirolimus and everolimus, have been approved for 
      use in metastatic RCC. Although relatively safe, these drugs are associated with 
      some unique adverse effects, such as hyperlipidemia, hyperglycemia, and 
      pneumonitis, that require monitoring and may require clinical intervention.
FAU - Borders, Emily B
AU  - Borders EB
AD  - College of Pharmacy, University of Oklahoma, Oklahoma City, OK 73117, USA. 
      emily-borders@ouhsc.edu
FAU - Bivona, Cory
AU  - Bivona C
FAU - Medina, Patrick J
AU  - Medina PJ
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Am J Health Syst Pharm
JT  - American journal of health-system pharmacy : AJHP : official journal of the 
      American Society of Health-System Pharmacists
JID - 9503023
RN  - 0 (Antineoplastic Agents)
RN  - 624KN6GM2T (temsirolimus)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/adverse effects/*pharmacology
MH  - Drug Delivery Systems
MH  - Drug Design
MH  - Drug Monitoring/methods
MH  - Drug Resistance, Neoplasm
MH  - Everolimus
MH  - Humans
MH  - Neoplasms/*drug therapy/pathology
MH  - Sirolimus/adverse effects/analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
EDAT- 2010/12/01 06:00
MHDA- 2011/03/15 06:00
CRDT- 2010/12/01 06:00
PHST- 2010/12/01 06:00 [entrez]
PHST- 2010/12/01 06:00 [pubmed]
PHST- 2011/03/15 06:00 [medline]
AID - 67/24/2095 [pii]
AID - 10.2146/ajhp100020 [doi]
PST - ppublish
SO  - Am J Health Syst Pharm. 2010 Dec 15;67(24):2095-106. doi: 10.2146/ajhp100020.