PMID- 35091825
OWN - NLM
STAT- MEDLINE
DCOM- 20220708
LR  - 20220708
IS  - 0171-2004 (Print)
IS  - 0171-2004 (Linking)
VI  - 272
DP  - 2022
TI  - Mechanistic Target of Rapamycin (mTOR) Inhibitors.
PG  - 53-72
LID - 10.1007/164_2021_553 [doi]
AB  - Mechanistic target of rapamycin (mTOR) inhibitors are macrocyclic lactone 
      antibiotics derived from Streptomyces hygroscopicus that prevent T lymphocyte 
      activation and B cell differentiation. Unlike calcineurin inhibitors (CNIs) that 
      inhibit cytokine production, mTOR inhibitors block the cytokine signal 
      transduction to arrest cells in the G1 to S phase. This class of drugs is 
      commonly used for post-transplantation and cancer management because of its 
      immunosuppressive and antiproliferative properties, respectively. The potential 
      uses of mTOR inhibitors are heavily explored because of their impact on cell 
      growth and proliferation. However, mTOR inhibitors have a broad range of effects 
      that can result in adverse reactions, but side effects can occur with other 
      immunosuppressive agents as well. Thus, the performance of mTOR inhibitors is 
      compared to the outcomes and adverse effects of other immunosuppressive drugs or 
      the combination of other immunosuppressants and mTOR inhibitors. Because mTOR 
      regulates many downstream pathways, mTOR inhibitors can affect these pathways to 
      manage various diseases. Sirolimus (rapamycin) is approved by the Food and Drug 
      Administration (FDA) to treat post-renal transplantation and 
      lymphangioleiomyomatosis (LAM). Everolimus is approved by the FDA to treat 
      postmenopausal advanced hormone receptor-positive, HER2-negative breast cancer in 
      women, progressive neuroendocrine tumors of pancreatic origin (PNET), advanced 
      renal cell carcinoma (RCC), renal angiomyolipoma (AML) and tuberous sclerosis 
      complex (TSC), and subependymal giant cell astrocytoma (SEGA) associated with TSC 
      as well as renal and liver transplantation. Temsirolimus is approved by the FDA 
      to treat advanced RCC. Opportunities to use mTOR inhibitors as therapy for other 
      transplantation, metabolic disease, and cancer management are being researched. 
      mTOR inhibitors are often called proliferation signal inhibitors (PSIs) because 
      of their effects on proliferation pathways.
CI  - (c) 2021. Springer Nature Switzerland AG.
FAU - Wang, Denise
AU  - Wang D
AD  - Mount Sinai Icahn School of Medicine, New York, NY, USA. iamdenisewang@gmail.com.
FAU - Eisen, Howard J
AU  - Eisen HJ
AD  - Pennsylvania State University College of Medicine/Milton S. Hershey Medical 
      Center, Hershey, PA, USA.
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Handb Exp Pharmacol
JT  - Handbook of experimental pharmacology
JID - 7902231
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
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  - *Angiomyolipoma/chemically induced/complications/drug therapy
MH  - *Carcinoma, Renal Cell/chemically induced/complications/drug therapy
MH  - Cytokines
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology/therapeutic use
MH  - *Kidney Neoplasms
MH  - Sirolimus/adverse effects
MH  - TOR Serine-Threonine Kinases
MH  - *Tuberous Sclerosis/chemically induced/complications/drug therapy
OTO - NOTNLM
OT  - Cancer immunosuppression
OT  - Graft rejection treatment
OT  - Proliferation signal inhibitors
OT  - Transplantation immunosuppression
EDAT- 2022/01/30 06:00
MHDA- 2022/07/09 06:00
CRDT- 2022/01/29 05:46
PHST- 2022/01/30 06:00 [pubmed]
PHST- 2022/07/09 06:00 [medline]
PHST- 2022/01/29 05:46 [entrez]
AID - 10.1007/164_2021_553 [doi]
PST - ppublish
SO  - Handb Exp Pharmacol. 2022;272:53-72. doi: 10.1007/164_2021_553.