The potential to target CCL5/CCR5 in breast cancer

Expert Opin Ther Targets. 2014 Nov;18(11):1265-75. doi: 10.1517/14728222.2014.949238. Epub 2014 Sep 26.

Abstract

Introduction: Chemokines play a crucial role in breast cancer tumorigenesis and progression. Recently, the chemokine (C-C motif) ligand 5 (CCL5), which can be secreted either by tumor cells or by mesenchymal stromal cells recruited to the tumor, has been identified as a key node in the bidirectional communication between breast cancer and normal cells.

Areas covered: In this review, the authors discuss the role of CCL5/chemokine receptor 5 (CCR5) axis in promoting breast cancer onset and progression. Interrogation of large clinical databases has demonstrated increased expression of the CCL5/CCR5 axis in specific subtypes of breast cancer. The activation of the receptor CCR5 in breast cancer cells controls their invasiveness serving as a driver for metastasis. Furthermore, the CCL5/CCR5 axis participates in the recruitment of specific immune cells into tumors, inducing local immunosuppression and favoring tumor progression.

Expert opinion: The role of CCR5 in HIV infection led to the development of specific and potent CCR5 antagonists. The data reviewed here includes basic and translational studies that support the use of such CCR5 antagonists in breast cancer patients as adjuvant therapy to block the metastasis.

Keywords: CCL5; breast cancer; chemokine receptor 5; maraviroc; mesenchymal stromal cells; metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • CCR5 Receptor Antagonists / pharmacology*
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Disease Progression
  • Drug Design
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism

Substances

  • Antineoplastic Agents
  • CCR5 Receptor Antagonists
  • Chemokine CCL5
  • Receptors, CCR5