Arachidonic acid metabolite as a novel therapeutic target in breast cancer metastasis

Thaiz Ferraz Borin, Kartik Angara, Mohammad H. Rashid, Bhagelu Ram Achyut, Ali Syed Arbab

Research output: Contribution to journalReview article

7 Citations (Scopus)

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.

Original languageEnglish (US)
Article number2661
JournalInternational journal of molecular sciences
Volume18
Issue number12
DOIs
StatePublished - Dec 8 2017

Fingerprint

metabolites
metastasis
Metabolites
Arachidonic Acid
breast
Tumors
cancer
Breast Neoplasms
Neoplasm Metastasis
acids
Acids
tumors
angiogenesis
therapy
Neoplasms
Cells
Metabolic Networks and Pathways
lungs
Therapeutics
Eicosanoids

Keywords

  • 20-HETE
  • Breast cancer metastasis
  • Cytochrome P450

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Arachidonic acid metabolite as a novel therapeutic target in breast cancer metastasis. / Borin, Thaiz Ferraz; Angara, Kartik; Rashid, Mohammad H.; Achyut, Bhagelu Ram; Arbab, Ali Syed.

In: International journal of molecular sciences, Vol. 18, No. 12, 2661, 08.12.2017.

Research output: Contribution to journalReview article

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