Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis
Metastatic breast cancer (BC) (also referred to as stage IV) spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor c...
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doaj-0ede3e6139554a689969f23fd6947c702020-11-24T21:53:03ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-12-011812266110.3390/ijms18122661ijms18122661Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer MetastasisThaiz F. Borin0Kartik Angara1Mohammad H. Rashid2Bhagelu R. Achyut3Ali S. Arbab4Tumor Angiogenesis Laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USATumor Angiogenesis Laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USATumor Angiogenesis Laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USATumor Angiogenesis Laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USATumor Angiogenesis Laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USAMetastatic breast cancer (BC) (also referred to as stage IV) spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4) family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE), an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis.https://www.mdpi.com/1422-0067/18/12/2661breast cancer metastasiscytochrome P45020-HETE |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thaiz F. Borin Kartik Angara Mohammad H. Rashid Bhagelu R. Achyut Ali S. Arbab |
spellingShingle |
Thaiz F. Borin Kartik Angara Mohammad H. Rashid Bhagelu R. Achyut Ali S. Arbab Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis International Journal of Molecular Sciences breast cancer metastasis cytochrome P450 20-HETE |
author_facet |
Thaiz F. Borin Kartik Angara Mohammad H. Rashid Bhagelu R. Achyut Ali S. Arbab |
author_sort |
Thaiz F. Borin |
title |
Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis |
title_short |
Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis |
title_full |
Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis |
title_fullStr |
Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis |
title_full_unstemmed |
Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis |
title_sort |
arachidonic acid metabolite as a novel therapeutic target in breast cancer metastasis |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-12-01 |
description |
Metastatic breast cancer (BC) (also referred to as stage IV) spreads beyond the breast to the bones, lungs, liver, or brain and is a major contributor to the deaths of cancer patients. Interestingly, metastasis is a result of stroma-coordinated hallmarks such as invasion and migration of the tumor cells from the primary niche, regrowth of the invading tumor cells in the distant organs, proliferation, vascularization, and immune suppression. Targeted therapies, when used as monotherapies or combination therapies, have shown limited success in decreasing the established metastatic growth and improving survival. Thus, novel therapeutic targets are warranted to improve the metastasis outcomes. We have been actively investigating the cytochrome P450 4 (CYP4) family of enzymes that can biosynthesize 20-hydroxyeicosatetraenoic acid (20-HETE), an important signaling eicosanoid involved in the regulation of vascular tone and angiogenesis. We have shown that 20-HETE can activate several intracellular protein kinases, pro-inflammatory mediators, and chemokines in cancer. This review article is focused on understanding the role of the arachidonic acid metabolic pathway in BC metastasis with an emphasis on 20-HETE as a novel therapeutic target to decrease BC metastasis. We have discussed all the significant investigational mechanisms and put forward studies showing how 20-HETE can promote angiogenesis and metastasis, and how its inhibition could affect the metastatic niches. Potential adjuvant therapies targeting the tumor microenvironment showing anti-tumor properties against BC and its lung metastasis are discussed at the end. This review will highlight the importance of exploring tumor-inherent and stromal-inherent metabolic pathways in the development of novel therapeutics for treating BC metastasis. |
topic |
breast cancer metastasis cytochrome P450 20-HETE |
url |
https://www.mdpi.com/1422-0067/18/12/2661 |
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