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Arachidonic Acid Metabolite as a Novel Therapeutic Target in Breast Cancer Metastasis
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 18, Iss 12, p 2661 (2017)
- Publication Year :
- 2017
- Publisher :
- MDPI AG, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
cytochrome P450
Angiogenesis
Breast Neoplasms
Review
Catalysis
Metastasis
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Immune system
breast cancer metastasis
Hydroxyeicosatetraenoic Acids
Tumor Microenvironment
medicine
Humans
Cytochrome P450 Family 4
Molecular Targeted Therapy
Neoplasm Metastasis
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Tumor microenvironment
Arachidonic Acid
Kinase
business.industry
Organic Chemistry
Cancer
General Medicine
medicine.disease
Metastatic breast cancer
3. Good health
Computer Science Applications
Review article
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
030220 oncology & carcinogenesis
Cancer research
Female
20-HETE
business
Signal Transduction
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....e1124c60daf29d1c678c796e7dfef3eb