Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/10132 |
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| author | Silviu Stanciu Florentina Ionita-Radu Constantin Stefani Daniela Miricescu Iulia-Ioana Stanescu-Spinu Maria Greabu Alexandra Ripszky Totan Mariana Jinga |
| author_facet | Silviu Stanciu Florentina Ionita-Radu Constantin Stefani Daniela Miricescu Iulia-Ioana Stanescu-Spinu Maria Greabu Alexandra Ripszky Totan Mariana Jinga |
| author_sort | Silviu Stanciu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:41:18Z |
| format | Article |
| id | doaj.art-5f1fc1577cdc4546828a14dc32ff6252 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:41:18Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5f1fc1577cdc4546828a14dc32ff62522023-11-23T13:23:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123171013210.3390/ijms231710132Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical AspectsSilviu Stanciu0Florentina Ionita-Radu1Constantin Stefani2Daniela Miricescu3Iulia-Ioana Stanescu-Spinu4Maria Greabu5Alexandra Ripszky Totan6Mariana Jinga7Department of Internal Medicine, Dr. Carol Davila Central Military Emergency University Hospital, 051075 Bucharest, RomaniaDepartment of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, 051075 Bucharest, RomaniaDepartment of Family Medicine and Clinical Base, Dr. Carol Davila Central Military Emergency University Hospital, 051075 Bucharest, RomaniaDepartment of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Biochemistry, Faculty of Dental Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, 051075 Bucharest, RomaniaAlthough 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.https://www.mdpi.com/1422-0067/23/17/10132pancreatic cancerrisk factorstumor microenvironmentPI3K/AKT/mTORinhibitors |
| spellingShingle | Silviu Stanciu Florentina Ionita-Radu Constantin Stefani Daniela Miricescu Iulia-Ioana Stanescu-Spinu Maria Greabu Alexandra Ripszky Totan Mariana Jinga Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects International Journal of Molecular Sciences pancreatic cancer risk factors tumor microenvironment PI3K/AKT/mTOR inhibitors |
| title | Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects |
| title_full | Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects |
| title_fullStr | Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects |
| title_full_unstemmed | Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects |
| title_short | Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects |
| title_sort | targeting pi3k akt mtor signaling pathway in pancreatic cancer from molecular to clinical aspects |
| topic | pancreatic cancer risk factors tumor microenvironment PI3K/AKT/mTOR inhibitors |
| url | https://www.mdpi.com/1422-0067/23/17/10132 |
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