PCSK9 and cancer: Rethinking the link
Background: Cancer is emerging as a major problem globally, as it accounts for the second cause of death despite medical advances. According to epidemiological and basic studies, cholesterol is involved in cancer progression and there are abnormalities in cholesterol metabolism of cancer cells inclu...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2021-08-01
|
Series: | Biomedicine & Pharmacotherapy |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332221005400 |
id |
doaj-6781e0a78bb641318c9aab9c90fadfff |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Khadijeh Mahboobnia Matteo Pirro Ettore Marini Francesco Grignani Evgeny E. Bezsonov Tannaz Jamialahmadi Amirhossein Sahebkar |
spellingShingle |
Khadijeh Mahboobnia Matteo Pirro Ettore Marini Francesco Grignani Evgeny E. Bezsonov Tannaz Jamialahmadi Amirhossein Sahebkar PCSK9 and cancer: Rethinking the link Biomedicine & Pharmacotherapy PCSK9 Cancer LDL cholesterol LDL receptor Monoclonal antibodies Vaccine |
author_facet |
Khadijeh Mahboobnia Matteo Pirro Ettore Marini Francesco Grignani Evgeny E. Bezsonov Tannaz Jamialahmadi Amirhossein Sahebkar |
author_sort |
Khadijeh Mahboobnia |
title |
PCSK9 and cancer: Rethinking the link |
title_short |
PCSK9 and cancer: Rethinking the link |
title_full |
PCSK9 and cancer: Rethinking the link |
title_fullStr |
PCSK9 and cancer: Rethinking the link |
title_full_unstemmed |
PCSK9 and cancer: Rethinking the link |
title_sort |
pcsk9 and cancer: rethinking the link |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-08-01 |
description |
Background: Cancer is emerging as a major problem globally, as it accounts for the second cause of death despite medical advances. According to epidemiological and basic studies, cholesterol is involved in cancer progression and there are abnormalities in cholesterol metabolism of cancer cells including prostate, breast, and colorectal carcinomas. However, the importance of cholesterol in carcinogenesis and thereby the role of cholesterol homeostasis as a therapeutic target is still a debated area in cancer therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9), a serine protease, modulates cholesterol metabolism by attachment to the LDL receptor (LDLR) and reducing its recycling by targeting the receptor for lysosomal destruction. Published research has shown that PCSK9 is also involved in degradation of other LDLR family members namely very-low-density-lipoprotein receptor (VLDLR), lipoprotein receptor-related protein 1 (LRP-1), and apolipoprotein E receptor 2 (ApoER2). As a result, this protein represents an interesting therapeutic target for the treatment of hypercholesterolemia. Interestingly, clinical trials on PCSK9-specific monoclonal antibodies have reported promising results with high efficacy in lowering LDL-C and in turn reducing cardiovascular complications. It is important to note that PCSK9 mediates several other pathways apart from its role in lipid homeostasis, including antiviral activity, hepatic regeneration, neuronal apoptosis, and modulation of various signaling pathways. Furthermore, recent literature has illustrated that PCSK9 is closely associated with incidence and progression of several cancers. In a number of studies, PCSK9 siRNA was shown to effectively suppress the proliferation and invasion of the several studied tumor cells. Hence, a novel application of PCSK9 inhibitors/silencers in cancer/metastasis could be considered. However, due to poor data on effectiveness and safety of PCSK9 inhibitors in cancer, the impact of PCSK9 inhibition in these pathological conditions is still unknown. Search methods: A vast literature search was conducted to find intended studies from 1956 up to 2020, and inclusion criteria were original peer-reviewed publications. Purpose of review: To date, PCSK9 has been scantly investigated in cancer. The question that needs to be discussed is “How does PCSK9 act in cancer pathophysiology and what are the risks or benefits associated to its inhibition?”. We reviewed the available publications highlighting the contribution of this proprotein convertase in pathways related to cancer, with focus on the potential implications of its long-term pharmacological inhibition in cancer therapy. |
topic |
PCSK9 Cancer LDL cholesterol LDL receptor Monoclonal antibodies Vaccine |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221005400 |
work_keys_str_mv |
AT khadijehmahboobnia pcsk9andcancerrethinkingthelink AT matteopirro pcsk9andcancerrethinkingthelink AT ettoremarini pcsk9andcancerrethinkingthelink AT francescogrignani pcsk9andcancerrethinkingthelink AT evgenyebezsonov pcsk9andcancerrethinkingthelink AT tannazjamialahmadi pcsk9andcancerrethinkingthelink AT amirhosseinsahebkar pcsk9andcancerrethinkingthelink |
_version_ |
1721371992170430464 |
spelling |
doaj-6781e0a78bb641318c9aab9c90fadfff2021-06-19T04:52:14ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-08-01140111758PCSK9 and cancer: Rethinking the linkKhadijeh Mahboobnia0Matteo Pirro1Ettore Marini2Francesco Grignani3Evgeny E. Bezsonov4Tannaz Jamialahmadi5Amirhossein Sahebkar6Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IranUnit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, ItalyUnit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, ItalyUnit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, ItalyLaboratory of Cellular and Molecular Pathology of Cardiovascular System, Institute of Human Morphology, 3 Tsyurupa Street, Moscow 117418, Russia; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow 125315, RussiaDepartment of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranApplied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Correspondence to: Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, P.O. Box: 91779-48564, Mashhad, Iranī.Background: Cancer is emerging as a major problem globally, as it accounts for the second cause of death despite medical advances. According to epidemiological and basic studies, cholesterol is involved in cancer progression and there are abnormalities in cholesterol metabolism of cancer cells including prostate, breast, and colorectal carcinomas. However, the importance of cholesterol in carcinogenesis and thereby the role of cholesterol homeostasis as a therapeutic target is still a debated area in cancer therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9), a serine protease, modulates cholesterol metabolism by attachment to the LDL receptor (LDLR) and reducing its recycling by targeting the receptor for lysosomal destruction. Published research has shown that PCSK9 is also involved in degradation of other LDLR family members namely very-low-density-lipoprotein receptor (VLDLR), lipoprotein receptor-related protein 1 (LRP-1), and apolipoprotein E receptor 2 (ApoER2). As a result, this protein represents an interesting therapeutic target for the treatment of hypercholesterolemia. Interestingly, clinical trials on PCSK9-specific monoclonal antibodies have reported promising results with high efficacy in lowering LDL-C and in turn reducing cardiovascular complications. It is important to note that PCSK9 mediates several other pathways apart from its role in lipid homeostasis, including antiviral activity, hepatic regeneration, neuronal apoptosis, and modulation of various signaling pathways. Furthermore, recent literature has illustrated that PCSK9 is closely associated with incidence and progression of several cancers. In a number of studies, PCSK9 siRNA was shown to effectively suppress the proliferation and invasion of the several studied tumor cells. Hence, a novel application of PCSK9 inhibitors/silencers in cancer/metastasis could be considered. However, due to poor data on effectiveness and safety of PCSK9 inhibitors in cancer, the impact of PCSK9 inhibition in these pathological conditions is still unknown. Search methods: A vast literature search was conducted to find intended studies from 1956 up to 2020, and inclusion criteria were original peer-reviewed publications. Purpose of review: To date, PCSK9 has been scantly investigated in cancer. The question that needs to be discussed is “How does PCSK9 act in cancer pathophysiology and what are the risks or benefits associated to its inhibition?”. We reviewed the available publications highlighting the contribution of this proprotein convertase in pathways related to cancer, with focus on the potential implications of its long-term pharmacological inhibition in cancer therapy.http://www.sciencedirect.com/science/article/pii/S0753332221005400PCSK9CancerLDL cholesterolLDL receptorMonoclonal antibodiesVaccine |