Publication
Title
RANK/RANKL signaling inhibition may improve the effectiveness of checkpoint blockade in cancer treatment
Author
Abstract
Binding between the receptor activator of nuclear factor-kB (RANK) and its ligand (RANKL) triggers recruitment of TNF receptor associated factor (TRAF) adaptor proteins and activation of downstream pathways. RANK/RANKL signaling is controlled by a decoy receptor called osteoprotegerin (OPG) which interacts with RANKL. Additional networks regulating RANK/RANKL signaling are active in a context specific manner. RANK/RANKL signaling is essential for the differentiation of bone-resorbing osteoclasts, and is deregulated in pathological processes such as postmenopausal osteoporosis or cancer induced bone destruction. Cells expressing RANK and RANKL are commonly found in the tumor microenvironment. The RANKL/RANK pathway is often overexpressed in tumors of the breast, prostate, endometrium, cervix, stomach, oesophagus and bladder, thyroid and correlated with poor prognosis. RANK signaling plays an important role in the innate and adaptive immune response as it generates regulatory T (Treg) cells and increases production of cytokines. RANK expression induces chemoresistance in vitro through the activation of multiple signal transduction pathways. RANKL blockade improves the efficacy of anti-CTLA-4 monoclonal antibodies against solid tumors and experimental metastases. As RANK inhibition enhances the immune response there is an increasing interest in combining it with immune therapy in an attempt to sensitize immune resistant tumors to immune therapies. Several studies are ongoing to assess this concept. The role of RANK/RANKL inhibition should be further pursued as an immunomodulatory strategy in combination with other treatment modalities.
Language
English
Source (journal)
Critical reviews in oncology, hematology / Chemical Rubber Company [Cleveland, Ohio] - Boca Raton, Fla
Publication
New york : Elsevier science inc , 2019
ISSN
1040-8428
DOI
10.1016/J.CRITREVONC.2018.10.011
Volume/pages
133 (2019) , p. 85-91
ISI
000457504300010
Pubmed ID
30661662
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 28.11.2018
Last edited 11.01.2024
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