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The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL

Authors :
Evangelos Koustas
Panagiotis Sarantis
Aristofania Simatou
Michalis V. Karamouzis
Athanasios G. Papavassiliou
Source :
International Journal of Molecular Sciences, Vol 21, Iss 7570, p 7570 (2020), International Journal of Molecular Sciences
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

The receptor activator of nuclear factor-κB (RANK) and the RANK ligand (RANKL) were reported in the regulation of osteoclast differentiation/activation and bone homeostasis. Additionally, the RANKL/RANK axis is a significant mediator of progesterone-driven mammary epithelial cell proliferation, potentially contributing to breast cancer initiation and progression. Moreover, several studies supported the synergistic effect of RANK and epidermal growth factor receptor (EGFR) and described RANK’s involvement in epidermal growth factor receptor 2 (ERBB2)-positive carcinogenesis. Consequently, anti-RANKL treatment has been proposed as a new approach to preventing and treating breast cancer and metastases. Recently, RANKL/RANK signaling pathway inhibition has been shown to modulate the immune environment and enhance the efficacy of anti-CTLA-4 and anti-PD-1 monoclonal antibodies against solid tumors. Clinical and experimental trials have emerged evaluating RANKL inhibition as an enhancer of the immune response, rendering resistant tumors responsive to immune therapies. Trials evaluating the combinatorial effect of immune checkpoint inhibitors and anti-RANKL treatment in double-positive (RANK+/ERBB2+) patients are encouraging.

Details

Language :
English
ISSN :
16616596 and 14220067
Volume :
21
Issue :
7570
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....19675980ce41afb2acd739c089cf2a97