Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma

Moschetta, Michele; Pietro, Giulia Di; Ria, Roberto; Gnoni, Antonio; Mangialardi, Giuseppe; Giacosa, Attilio; Ditonno, Paolo; Musto, Pellegrino; D’Auria, Fiorella; Ricciardi, Maria Rosaria; Dammacco, Franco; Ribatti, Doménico; Vacca, Angelo

doi:10.1016/j.ejca.2009.10.019

Cited by 61 publications

(48 citation statements)

References 34 publications

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“…RANKL-secreting osteoblasts can activate osteoclasts, leading to bone resorption. For that reason, several bone-targeted agents have been developed, most notably bisphosphonates, which are highly effective at stabilizing the bone and preventing skeletal complications (73)(74)(75).…”

Section: Agents Under Developmentmentioning

confidence: 99%

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

et al. 2012

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Abstract. Prostate cancer is the most common cancer in men in Europe and the United States, and the third leading cause of death from cancer in Europe. Survival of prostate cancer cells is dependent on the activation of androgen receptors (AR), that are overexpressed in this tumor. Furthermore, ~90% of prostate cancer patients that respond to first-line androgen deprivation therapy (ADT) undergo rapid progression. This condition is defined as castration-resistant prostate cancer (CRPC). Docetaxelbased regimens significantly improve overall survival (OS) in patients with CRPC and represent the only treatment strategy approved by the Food and Drug Administration (FDA). Recently, abiraterone (second hormonal therapy) and cabazitaxel (new taxane) have been shown to improve survival in patients with CRPC who progressed following docetaxel-based chemotherapy. Vaccine therapy has also been demonstrated to improve OS in patients with asymptomatic or minimally symptomatic metastatic CRPC. Additional therapeutic targets have been analyzed in prostate cancer, including apoptosis, angiogenic receptors, vitamin D and Src pathways. Several phase II studies are ongoing. The high frequency of prostate cancer-related metastatic bone disease has led to consider this pathway as a therapeutic target. To this end, several bone-targeted agents have been investigated, most notably zoledronic acid, which is highly effective at stabilizing the bone and preventing skeletal complications. More recently, a nuclear factor-β ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases.

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Section: Agents Under Developmentmentioning

confidence: 99%

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

et al. 2012

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“…In vivo N-BPs may also affect MM progression by blocking the release of cytokines and growth factors from the bone matrix, thereby breaking the vicious cycle of bone destruction and cancer growth [74]. In addition, the anticancer effects of BPs have been demonstrated to have synergy with agents that are used in the treatment of myeloma, including dexamethasone, thalidomide, and bortezomib [84,87,88]. Preclinical mouse models of MM indicate that the anti-myeloma effect of N-BPs may be mediated via the inhibition of protein prenylation and consequent inhibition of the RAS-RAF-MAPK pathway [89], a mechanism of action not shared by non-N-BPs.…”

Section: Bisphosphonates (Bps)mentioning

confidence: 98%

Targeting Bone as a Therapy for Myeloma

Morgan

2011

Cancer Microenvironment

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Myeloma bone disease (BD) not only impairs quality of life, but is also associated with impaired survival. Studies of the biology underlying BD support the notion that the increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and a necessity for tumour growth and clonal expansion. Survival and expansion of the myeloma clone is dependent on its interactions with bone elements, thus targeting these interactions should have antimyeloma activities. Indeed both experimental and clinical findings indicate that bone-targeted therapies not only improve BD, but also create an inhospitable environment for myeloma cell growth and survival, favouring improved clinical outcome. This review summarizes recent progress in our understandings of the biology of myeloma BD, highlighting the role of osteoclasts and osteoblasts in this process and how they can be targeted therapeutically. Unravelling the mechanisms underlying myeloma-bone interactions will facilitate the development of novel therapeutic agents to treat BD, which as a consequence are likely to improve the clinical outcome of myeloma patients.

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“…The mechanism of this effect is unknown, but we can deduce that zoledronic acid may elicite several angiogenic-related cytokines patterns and cascades, as demonstrated by preclinical studies. About our study, even if it was a pilot study, there are some limitation based on the low number of patients enrolled and the brief period of monitoring cytokines levels [25].…”

Section: Discussionmentioning

confidence: 99%

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

Annibali¹,

Petrucci²,

Tirindelli³

et al. 2017

J Blood Lymph

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Objective: Multiple Myeloma (MM) is characterized by uncoupling of bone resorption from bone formation which leads to the predominance of resorption. Bisphosphonates are chemical compounds that selectively concentrate at the interface of the active osteoclasts and the bone resorption surface where they inhibit osteoclast activity. Aim of this study was to describe cytokines behaviour in MM and to evaluate whether zoledronic acid could have an in vivo anti-angiogenic property in MM as observed in solid tumours.Methods: Serum samples from 29 (16 males and 13 females) consecutive MM patients with lytic bone lesions treated with 4 mg of zoledronic acid were tested for platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF α) and insulin growth factor (IGF-I). Basal cytokine levels were compared with the values observed after 1, 2, 7 and 21 days of treatment, using the Wilcoxon's test for nonparametric-dependent continuous variables.Results: A significant increase in IL-6 and TNF α was observed on days 1 and 2. As for VEGF, the levels of this cytokine did not change significantly from basal values during the entire period of observation except for a significant increase day 7 (P=0.0005). Moreover, PDGF significantly decreased (P=0.005) after 2 days from zoledronic acid infusion. Conclusions:From this study appears that in MM, treatment with zoledronic acid induces a transient reduction in PDGF according with previous studies in solid cancer, while the increase of IL-6 and VEGF could be related through a paracrine mechanism. The anti-myeloma effect of this drug could be driven through this mechanism.

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Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma

Cited by 61 publications

References 34 publications

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

Novel strategies in the treatment of castration-resistant prostate cancer (Review)

Targeting Bone as a Therapy for Myeloma

Cytokines Behavior in Multiple Myeloma Patients during Zoledronic Acid Treatment

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