Τίτλος:
The role of the RANKL/RANK axis in the prevention and treatment of breast cancer with immune checkpoint inhibitors and anti-RANKL
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020 by the authors.
Συγγραφείς:
Simatou, A.
Sarantis, P.
Koustas, E.
Papavassiliou, A.G.
Karamouzis, M.V.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
aromatase inhibitor; bisphosphonic acid derivative; calcium; checkpoint kinase inhibitor; denosumab; epidermal growth factor receptor; immunoglobulin enhancer binding protein; osteoclast differentiation factor; pamidronic acid; radium chloride ra 223; vitamin D; zoledronic acid; epidermal growth factor receptor 2; osteoclast differentiation factor; receptor activator of nuclear factor kappa B, breast cancer; breast carcinogenesis; breast development; cancer cell; cancer growth; cancer immunotherapy; cancer prevention; cancer resistance; cancer survival; cell proliferation; human; immune response; immunomodulation; metastasis; Review; signal transduction; animal; breast tumor; female; metabolism; pharmacology; signal transduction, Animals; Breast Neoplasms; Female; Humans; Immune Checkpoint Inhibitors; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptor, ErbB-2; Signal Transduction
DOI:
10.3390/ijms21207570