The Non-Bone-Related Role of RANK/RANKL Signaling in Cancer

Dam, Peter van; Verhoeven, Yannick; Trinh, Xuan Bich

doi:10.1007/978-3-030-50224-9_3

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…Many studies have shown that the RANK/RANKL system plays an essential role in developmental maturation and functional maintenance of the immune system. By genetically engineering RANK- or RANKL-deficient mice, it has been found that RANKL knock out mice show lymph node deficiency and impaired B-cell development ( 38 , 39 ), and patients with mutations in the TNFRSF11A gene (encoding RANK) show a significant reduction in B-cell numbers ( 40 ), which confirms that RANK/RANKL is essential for early T cell and B cell development. In addition, RANK/RANKL intervenes in the interactions between T cells and dendritic cells s, and RANKL enhances dendritic cell formation and function in the absence of co-stimulation and antigen presentation, enhancing the ability of dendritic cells to stimulate the proliferation and differentiation of naive T cells ( 41 ).…”

Section: Introductionmentioning

confidence: 85%

“…Although it is not clear whether the RANK/RANKL signaling pathway plays a favorable or unfavorable role in tumor proliferation and metabolism, there is no doubt that RANK/RANKL signaling plays a very important role in tumors. RANK/RANKL is expressed in many tumor tissues ( 39 ), and many breast cancer patients show abnormally high levels of RANKL expression in primary lesions, and a positive correlation with the incidence of bone metastases ( 47 ). RANK/RANKL is directly involved in tumor proliferation and metabolism and regulates the tumor immune microenvironment ( 48 ).…”

Section: Introductionmentioning

confidence: 99%

“…Does it have an effect on effectiveness or does it produce drug resistance? Studies in animal models have shown that inhibition of RANKL improves the efficacy of the chemotherapeutic agent cisplatin, but there are no objective data on the effect of denosumab in combination with chemotherapeutic agents at this time ( 39 ).…”

Section: Introductionmentioning

confidence: 99%

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Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials

Zhang

et al. 2023

Front. Oncol.

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Denosumab, a fully humanized monoclonal neutralizing antibody, inhibits activation of the RANK/RANKL/OPG signaling pathway through competitive binding with RANKL, thereby inhibiting osteoclast-mediated bone resorption. Denosumab inhibits bone loss; therefore, it is used to treat metabolic bone diseases (including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis), in clinical practice. Since then, multiple effects of denosumab have been discovered. A growing body of evidence suggests that denosumab has a variety of pharmacological activities and broad potential in clinical diseases such as osteoarthritis, bone tumors, and other autoimmune diseases. Currently, Denosumab is emerging as a treatment for patients with malignancy bone metastases, and it also shows direct or indirect anti-tumor effects in preclinical models and clinical applications. However, as an innovative drug, its clinical use for bone metastasis of malignant tumors is still insufficient, and its mechanism of action needs to be further investigated. This review systematically summarizes the pharmacological mechanism of action of denosumab and the current understanding and clinical practice of the use of denosumab for bone metastasis of malignant tumors to help clinicians and researchers deepen their understanding of denosumab.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials

Zhang

et al. 2023

Front. Oncol.

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“…They are shown effective as the adjuvant therapy of solid tumors, including prostatic cancer (PC), melanoma and non-small cell lung cancer (NSCLC) [ 11 , 12 ]. Recent evidence has demonstrated that anti-RANKL can enhance the effect of ICIs against solid tumors and metastases [ 13 , 14 ]. A combination of BMAs (whether ZA or denosumab) and ICI/TKIs can improve clinical outcomes [ 12 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Combination of Bone-Modifying Agents with Immunotarget Therapy for Hepatocellular Carcinoma with Bone Metastases

Chen

Shen

Wang

et al. 2022

JCM

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Due to limited investigations about efficacy of tyrosine kinase inhibitors (TKIs) plus immune-checkpoint inhibitors (ICIs) versus TKIs alone, and effects of durations of bone modifying agents (BMAs) on the survival of patients with hepatocellular carcinoma (HCC) and bone metastases (BoM), we aim to compare the efficacy of TKIs both alone and in combination with ICIs, as well as comparing long-term and no or perioperative use of BMAs for patients with HCC and BoM. Patients with pathologically confirmed HCC and BoM were included in the study. They were stratified into the TKIs group and the TKIs + ICIs group, and the perioperative and the long-term use of BMAs group. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to assess the response to these regimes. The cumulative risk of initial skeletal-related events (SREs) was used to evaluate treatment efficacy for bone lesions. A total of 21 (33.9%) patients received TKIs (Sorafenib or Lenvatinib) alone and 41 (66.1%) received TKIs + ICIs. The combination group showed higher ORR than monotherapy group (1/21, 4.7% vs. 9/41, 22.0%; p = 0.1432); Additionally, the TKIs + ICIs group offered improved OS (18 months vs. 31 months; p = 0.015) and PFS (10 months vs. 23 months; p = 0.014), while this survival benefits were more profound in virus-infected patients than those non-infected. Prolonged OS (33 months vs. 16 months; p = 0.0048) and PFS (33 months vs. 11 months; p = 0.0027) were observed in patients with long-term use of BMAs compared with no or perioperative use of BMAs. The TKIs + ICIs combination and long-term adjuvant of BMAs may offer a survival advantage for HCC patients with BoM without severe adverse events, which requires further validations.

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Infectious Osteomyelitis: Marrying Bone Biology and Microbiology to Shed New Light on a Persistent Clinical Challenge

Veis

Cassat

2020

Journal of Bone and Mineral Research

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Infections of bone occur in a variety of clinical settings, ranging from spontaneous isolated infections arising from presumed hematogenous spread to those associated with skin and soft tissue wounds or medical implants. The majority are caused by the ubiquitous bacterium Staphyloccocus (S.) aureus, which can exist as a commensal organism on human skin as well as an invasive pathogen, but a multitude of other microbes are also capable of establishing bone infections. While studies of clinical isolates and small animal models have advanced our understanding of the role of various pathogen and host factors in infectious osteomyelitis (iOM), many questions remain unaddressed. Thus, there are many opportunities to elucidate host‐pathogen interactions that may be leveraged toward treatment or prevention of this troublesome problem. Herein, we combine perspectives from bone biology and microbiology and suggest that interdisciplinary approaches will bring new insights to the field. © 2021 American Society for Bone and Mineral Research (ASBMR).

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The Non-Bone-Related Role of RANK/RANKL Signaling in Cancer

Cited by 5 publications

References 58 publications

Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials

Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials

Combination of Bone-Modifying Agents with Immunotarget Therapy for Hepatocellular Carcinoma with Bone Metastases

Infectious Osteomyelitis: Marrying Bone Biology and Microbiology to Shed New Light on a Persistent Clinical Challenge

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