The therapeutic potential of renin-angiotensin system inhibitors in the treatment of pancreatic cancer

Khoshghamat, Negar; Jafari, Niloufar; Toloue-pouya, Vajiheh; Azami, Shakiba; Mirnourbakhsh, Seyyedeh Helya; Khazaei, Majid; Rajabian, Majid

doi:10.1016/j.lfs.2021.119118

Cited by 13 publications

(10 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We showed that the RAS signaling pathways that are connected to cytoskeletal remodeling, endocytosis, mitogen-activated protein kinase (MAPK) pathways, T-cell receptor signaling pathways, and PI3K-Akt signaling pathways, are play a critical mechanistic pathways in OSBPL-expressing PDAC. The RAS pathway was also reported to modulate tumor growth, angiogenesis, and tumor metastasis in pancreatic cancer [ 57 ]. Taken together, OSBPL3 might play a crucial role in tumorigenesis through regulating several critical signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Potential Prognostic Biomarkers of OSBPL Family Genes in Patients with Pancreatic Ductal Adenocarcinoma

Chou

Hsieh

et al. 2021

Biomedicines

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal malignancy with poor survival outcomes. In addition, oxysterol-binding protein-like (OSBPL) family members are reported to be involved in lipid binding and transport and play critical roles in tumorigenesis. However, relationships between PDAC and OSBPL family members have not comprehensively been elucidated. In this study, we used the Oncomine and GEPIA 2 databases to analyze OSBPL transcription expressions in PDAC. The Kaplan–Meier plotter and TIMER 2.0 were used to assess the relationships between overall survival (OS) and immune-infiltration with OSBPL family members. Co-expression data from cBioPortal were downloaded to assess the correlated pathways with OSBPL gene family members using DAVID. The expressions of OSBPL3, OSBPL8, OSBPL10, and OSBPL11 were found to be highly upregulated in PDAC. Low expressions of OSBPL3, OSBPL8, and OSBPL10 indicated longer OS. The functions of OSBPL family members were mainly associated with several potential signaling pathways in cancer cells, including ATP binding, integrin binding, receptor binding, and the renin-angiotensin system (RAS) signaling pathway. The transcription levels of OSBPL gene family members were connected with several immune infiltrates. Collectively, OSBPL family members are influential biomarkers for the early diagnosis of PDAC and have prognostic value, with the promise of precise treatment of PDAC in the future.

show abstract

Section: Discussionmentioning

confidence: 99%

Potential Prognostic Biomarkers of OSBPL Family Genes in Patients with Pancreatic Ductal Adenocarcinoma

Chou

Hsieh

et al. 2021

Biomedicines

View full text Add to dashboard Cite

show abstract

“…However, our results indicate that it may be safer to treat hypertension in smokers using an ACEi that may decrease the HL concentration rather than ARB that may increase it. This issue should be carefully explored because both drug classes have been recently proposed not only as anti-hypertensives but also as potential adjuvants for anti-cancer therapy [ 69 , 70 , 71 , 72 ]. Furthermore, they may be beneficial as an add-on treatment for COVID-19 [ 73 ] and may lower the risk of developing neurodegenerative conditions, such as Parkinson’s and Alzheimer’s disease [ 74 , 75 ].…”

Section: Resultsmentioning

confidence: 99%

Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide

et al. 2023

View full text Add to dashboard Cite

Tobacco smoking is deleterious to the lungs because it exposes them to many toxic substances. These include transition metal ions, such as cadmium. However, there is a lack of information about the influence of endogenous metal-binding peptides, such as His-Leu (HL), on the lung distribution of transition metals in smokers. To address this, we administered HL subcutaneously to rats exposed to tobacco smoke for six weeks, then we measured the concentrations of transition metal ions in the lungs. We found that exposure to tobacco smoke elevates the concentrations of Cd(II) and Cu(II). Administration of the HL peptide, whose elevation is a consequence of angiotensin receptor blocker anti-hypertension therapy, increases the concentration of Fe in the lungs of rats exposed to smoke. These findings suggest that smoking is a risk factor for patients receiving angiotensin receptor blockers to treat hypertension.

show abstract

“…This, in turn, leads to an increased secretion of tumor growth factors that boost both cell proliferation and growth of stromal cells, as well as tumor angiogenesis by up-regulating vascular endothelial growth factor (VEGF) expression [151][152][153][154]. Based on these considerations, losartan was extensively tested in different preclinical tumor models, including pancreatic cancer, for its anti-angiogenic, anti-fibrotic and thus anti-neoplastic potential [155][156][157][158]. In particular, a study pointed out an improved survival benefit in rat orthotopic pancreatic cancer models treated with a combination of losartan and gemcitabine through a mechanism involving the inhibition of VEGF synthesis and suppression of PC cell proliferation via AT1R blockade [54].…”

Section: Losartanmentioning

confidence: 99%

Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates

Lellis

Veschi

Tinari

et al. 2021

Cancers

View full text Add to dashboard Cite

Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, since patients rarely display symptoms until an advanced and unresectable stage of the disease. Current chemotherapy options are unsatisfactory and there is an urgent need for more effective and less toxic drugs to improve the dismal PC therapy. Repurposing of non-oncology drugs in PC treatment represents a very promising therapeutic option and different compounds are currently being considered as candidates for repurposing in the treatment of this tumor. In this review, we provide an update on some of the most promising FDA-approved, non-oncology, repurposed drug candidates that show prominent clinical and preclinical data in pancreatic cancer. We also focus on proposed mechanisms of action and known molecular targets that they modulate in PC. Furthermore, we provide an explorative bioinformatic analysis, which suggests that some of the PC repurposed drug candidates have additional, unexplored, oncology-relevant targets. Finally, we discuss recent developments regarding the immunomodulatory role displayed by some of these drugs, which may expand their potential application in synergy with approved anticancer immunomodulatory agents that are mostly ineffective as single agents in PC.

show abstract

The therapeutic potential of renin-angiotensin system inhibitors in the treatment of pancreatic cancer

Cited by 13 publications

References 55 publications

Potential Prognostic Biomarkers of OSBPL Family Genes in Patients with Pancreatic Ductal Adenocarcinoma

Potential Prognostic Biomarkers of OSBPL Family Genes in Patients with Pancreatic Ductal Adenocarcinoma

Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide

Drug Repurposing, an Attractive Strategy in Pancreatic Cancer Treatment: Preclinical and Clinical Updates

Contact Info

Product

Resources

About