4.5 Review

The potential to target CCL5/CCR5 in breast cancer

Journal

EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 18, Issue 11, Pages 1265-1275

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2014.949238

Keywords

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

Funding

  1. PAPIIT-UNAM [IN219613]
  2. CONACYT [225313]
  3. Instituto Cientifico Pfizer, Mexico
  4. NIH [R01CA070896, R01CA075503, R01CA132115, R01CA107382, R01CA08 6072]
  5. Kimmel Cancer Center NIH Cancer Center [P30CA056036]
  6. Dr. Ralph and Marian C. Falk Medical Research Trust
  7. Margaret Q. Landenberger Research Foundation
  8. Pennsylvania Department of Health

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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.

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