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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
- 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.
- Subjects :
- musculoskeletal diseases
Receptor, ErbB-2
EGFR
Breast Neoplasms
Review
medicine.disease_cause
RANK
Catalysis
Inorganic Chemistry
immune checkpoint inhibitors
lcsh:Chemistry
Immune system
Osteoclast
Animals
Humans
Medicine
Epidermal growth factor receptor
Physical and Theoretical Chemistry
ERBB2
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Receptor Activator of Nuclear Factor-kappa B
biology
business.industry
RANK Ligand
Organic Chemistry
RANKL
denosumab
General Medicine
Computer Science Applications
Denosumab
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Cancer research
Female
Signal transduction
business
Carcinogenesis
Signal Transduction
medicine.drug
Subjects
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