PMID- 36077529
OWN - NLM
STAT- MEDLINE
DCOM- 20220912
LR  - 20240102
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 17
DP  - 2022 Sep 4
TI  - Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to 
      Clinical Aspects.
LID - 10.3390/ijms231710132 [doi]
LID - 10132
AB  - Although pancreatic cancer (PC) was considered in the past an orphan cancer type 
      due to its low incidence, it may become in the future one of the leading causes 
      of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent 
      type of PC, being a highly aggressive malignancy and having a 5-year survival 
      rate of less than 10%. Non-modifiable (family history, age, genetic 
      susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, 
      diabetes mellitus, intestinal microbiota) risk factors are involved in PC 
      pathogenesis. Chronic inflammation induced by various factors plays crucial roles 
      in PC development from initiation to metastasis. In multiple malignant conditions 
      such as PC, cytokines, chemokines, and growth factors activate the class I 
      phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of 
      rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell 
      growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, 
      and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual 
      inhibitors are being tested in vitro and in vivo with promising results for PC 
      patients. The main aim of this review is to present PC incidence, risk factors, 
      tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and 
      inhibitors used in clinical, in vivo, and in vitro studies.
FAU - Stanciu, Silviu
AU  - Stanciu S
AD  - Department of Internal Medicine, Dr. Carol Davila Central Military Emergency 
      University Hospital, 051075 Bucharest, Romania.
FAU - Ionita-Radu, Florentina
AU  - Ionita-Radu F
AUID- ORCID: 0000-0001-9829-5035
AD  - Department of Gastroenterology, Dr. Carol Davila Central Military Emergency 
      University Hospital, 051075 Bucharest, Romania.
FAU - Stefani, Constantin
AU  - Stefani C
AD  - Department of Family Medicine and Clinical Base, Dr. Carol Davila Central 
      Military Emergency University Hospital, 051075 Bucharest, Romania.
FAU - Miricescu, Daniela
AU  - Miricescu D
AD  - Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University 
      of Medicine and Pharmacy, 050474 Bucharest, Romania.
FAU - Stanescu-Spinu, Iulia-Ioana
AU  - Stanescu-Spinu II
AD  - Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University 
      of Medicine and Pharmacy, 050474 Bucharest, Romania.
FAU - Greabu, Maria
AU  - Greabu M
AD  - Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University 
      of Medicine and Pharmacy, 050474 Bucharest, Romania.
FAU - Ripszky Totan, Alexandra
AU  - Ripszky Totan A
AUID- ORCID: 0000-0002-4345-282X
AD  - Department of Biochemistry, Faculty of Dental Medicine, Carol Davila University 
      of Medicine and Pharmacy, 050474 Bucharest, Romania.
FAU - Jinga, Mariana
AU  - Jinga M
AD  - Department of Gastroenterology, Dr. Carol Davila Central Military Emergency 
      University Hospital, 051075 Bucharest, Romania.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220904
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Proliferation
MH  - Humans
MH  - *Pancreatic Neoplasms/metabolism
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Microenvironment
PMC - PMC9456549
OTO - NOTNLM
OT  - PI3K/AKT/mTOR
OT  - inhibitors
OT  - pancreatic cancer
OT  - risk factors
OT  - tumor microenvironment
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/10 06:00
MHDA- 2022/09/14 06:00
PMCR- 2022/09/04
CRDT- 2022/09/09 01:09
PHST- 2022/08/09 00:00 [received]
PHST- 2022/09/01 00:00 [revised]
PHST- 2022/09/01 00:00 [accepted]
PHST- 2022/09/09 01:09 [entrez]
PHST- 2022/09/10 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/09/04 00:00 [pmc-release]
AID - ijms231710132 [pii]
AID - ijms-23-10132 [pii]
AID - 10.3390/ijms231710132 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Sep 4;23(17):10132. doi: 10.3390/ijms231710132.