Bone targeted therapy for preventing skeletal-related events in metastatic breast cancer

Irelli, Azzurra; Cocciolone, Valentina; Cannita, Katia; Zugaro, Luigi; Staso, Mario Di; Baldi, Paola Lanfiuti; Paradisi, Stefania; Sidoni, Tina; Ricevuto, Enrico; Ficorella, Corrado

doi:10.1016/j.bone.2016.04.006

Cited by 16 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, bone modifying agents, including bisphosphonates and denosumab, can prevent and treat SREs by inhibiting osteoclast formation and bone degradation and have been viewed as an indispensable therapy for breast cancer patients with bone metastasis [ 37 ]. Moreover, meta-analyses have verified that adjuvant bisphosphonates reduce the rate of breast cancer recurrence in bone and improve breast cancer survival, but the benefit is only observed in women who were postmenopausal at the onset of treatment [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11

et al. 2018

View full text Add to dashboard Cite

BackgroundMost patients with breast cancer in advanced stages of the disease suffer from bone metastases which lead to fractures and nerve compression syndromes. microRNA dysregulation is an important event in the metastases of breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer has not been reported. Therefore, this study aimed to investigate the role and underlying mechanism of miR-124 in bone metastases of breast cancer.MethodsIn situ hybridization (ISH) was used to detect the expression of miR-124 in breast cancer tissues and bone metastatic tissues. Ventricle injection model was constructed to explore the effect of miR-124 on bone metastasis in vivo. The function of cancer cell derived miR-124 in the differentiation of osteoclast progenitor cells was verified in vitro. Dual-luciferase reporter assay was conducted to confirm Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in the prognosis of breast cancer patients with bone metastasis was determined by Kaplan-Meier analysis.ResultsHerein, we found that miR-124 was significantly reduced in metastatic bone tissues from breast cancers. Down-regulation of miR-124 was associated with aggressive clinical characteristics and shorter bone metastasis-free survival and overall survival. Restoration of miR-124 suppressed, while inhibition of miR-124 promoted the bone metastasis of breast cancer cells in vivo. At the cellular level, gain of function and loss-of function assays indicated that cancer cell-derived miR-124 inhibited the survival and differentiation of osteoclast progenitor cells. At the molecular level, we demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR-124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely correlated with miR-124, and up-regulation IL-11 in bone metastases was associated with a poor prognosis.ConclusionsThus, the identification of a dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer metastases to bone, uncovers new prognostic markers, and facilitates the development of novel therapeutic targets to treat and even prevent bone metastases of breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12943-017-0746-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The increase in bone turnover, also favored by a low dietary intake of calcium and vitamin D deficiency, promotes the growth of the tumor in the bone. During the metastatic process, the components deriving from bone metabolism, generally identified as formation markers (e.g., PINP and PICP) and bone resorption (e.g., NTx and CTx), are released into the bloodstream [27]. PTH induces osteoblasts to secrete macrophage colony-stimulating factor (M-CSF) and RANKL; both induce monocytes to differentiate into osteoclasts.…”

Section: Mtor and Bone Metabolismmentioning

confidence: 99%

mTOR Links Tumor Immunity and Bone Metabolism: What are the Clinical Implications?

Irelli

Sirufo

Scipioni

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) plays a crucial role in the control of cellular growth, proliferation, survival, metabolism, angiogenesis, transcription, and translation. In most human cancers, alterations to this pathway are common and cause activation of other downstream signaling pathways linked with oncogenesis. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both tumor immunity and angiogenesis. Inflammation is a hallmark of cancer, playing a central role in the tumor dynamics, and immune cells can exert antitumor functions or promote the growth of cancer cells. In this context, mTOR may regulate the activity of macrophages and T cells by regulating the expression of cytokines/chemokines, such as interleukin (IL)-10 and transforming growth factor (TGF-β), and/or membrane receptors, such as cytotoxic T-Lymphocyte protein 4 (CTLA-4) and Programmed Death 1 (PD-1). Furthermore, inhibitors of mammalian target of rapamycin are demonstrated to actively modulate osteoclastogenesis, exert antiapoptotic and pro-differentiative activities in osteoclasts, and reduce the number of lytic bone metastases, increasing bone mass in tumor-bearing mice. With regard to the many actions in which mTOR is involved, the aim of this review is to describe its role in the immune system and bone metabolism in an attempt to identify the best strategy for therapeutic opportunities in the metastatic phase of solid tumors.

show abstract

“…Nowadays, radiotherapy, surgery as well as systemic drug therapies (chemotherapy, hormone therapy), and targeted therapy are effective clinical therapies for osteolysis. The efficacy of BP appeared to be time-dependent and they were effective after 6-12 months of therapy (Irelli et al, 2016). Denosumab is a kind of human monoclonal antibody that combines especially with RANKL to inhibit the activation of osteoclasts.…”

Section: Osteolytic Cancer Bone Metastasismentioning

confidence: 99%

“…Bone metastasis and concomitant complications are huge challenges for cancer treatment in the clinic. Bone metastases occur in about 70% of patients suffering from advanced breast cancer or prostate cancer and approximately 15-30% of patients with carcinoma of the lung, colon, stomach, bladder, uterus, rectum, thyroid, or kidney (Irelli et al, 2016;Sun, Han, et al, 2016). Escaping from the tumor in-situ, tumor cells enter circulation through blood vessels and lymph vessels and then travel all over the body to find fertile soil to proliferate (Croucher et al, 2016;Vinay & KusumDevi, 2016;Chen, Pei, et al, 2018;Ahangar et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

Cheng

Wei

et al. 2020

Drug Delivery

View full text Add to dashboard Cite

Bone targeted therapy for preventing skeletal-related events in metastatic breast cancer

Cited by 16 publications

References 41 publications

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11

microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin-11

mTOR Links Tumor Immunity and Bone Metabolism: What are the Clinical Implications?

The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

Contact Info

Product

Resources

About