Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction

Yamakawa, Yasuaki; Tazawa, Hiroshi; Hasei, Joe; Osaki, Shuhei; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Uotani, Kouji; Fujiwara, Tomohiro; Yoshida, Aki; Urata, Yasuo; Kagawa, Shunsuke

doi:10.1111/cas.13316

Cited by 14 publications

(12 citation statements)

References 46 publications

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“…This process maintains a balance between the death and survival of cells and tissues [ 56 ]. It is demonstrated that ZA induces the apoptosis of osteoclasts through inhibition of the farnesyl pyrophosphate synthase (FPPS)-mediated mevalonate pathway, and induction of reactive oxygen species (ROS)-mediated apoptosis [ 24 , 39 , 57 , 58 ].…”

Section: Induction Of Apoptosis Of Osteoclastsmentioning

confidence: 99%

“…Furthermore, it is demonstrated that the treatment of ZA with other chemotherapies in children leukemia related osteonecrosis is safe and tolerant [ 118 ]. Combination therapy with ZA and tumor-specific replicating oncolytic adenovirus DBP-301 significantly inhibits tumor-mediated osteoclast activation, tumor growth and bone destruction via suppression of Mcl-1 [ 24 ]. In addition, ZA and R115777 (Zarnestra) are synergistic in inducing both growth inhibition and apoptosis in cancer cells by disruption of Ras-dependent Erk and Akt survival pathways and consequent Bcl-related proteins-dependent apoptosis [ 76 , 78 ].…”

Section: Anticancer Effects Of Zamentioning

confidence: 99%

“…ZA is the most widely used BP for its potent anti-resorptive activity, in addition, it inhibits the differentiation and apoptosis of osteoclasts [ 17 – 19 ]. It also has anticancer effects [ 15 , 20 ], including suppressing metastasis of cancer [ 21 , 22 ], inhibiting the angiogenesis [ 23 ], and the synergistic effect with other anticancer drugs [ 17 , 20 , 24 ]. Here, we want to elaborate the mechanisms of ZA in inhibition of differentiation and apoptosis of osteoclasts, as well as its anticancer effects, which may provide a new strategy for the treatment of cancer, especially cancer with bone metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review

Wang

Fang

et al. 2020

BMC Cancer

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Zoledronic acid (ZA) is one of the most important and effective class of anti-resorptive drug available among bisphosphonate (BP), which could effectively reduce the risk of skeletal-related events, and lead to a treatment paradigm for patients with skeletal involvement from advanced cancers. However, the exact molecular mechanisms of its anticancer effects have only recently been identified. In this review, we elaborate the detail mechanisms of ZA through inhibiting osteoclasts and cancer cells, which include the inhibition of differentiation of osteoclasts via suppressing receptor activator of nuclear factor κB ligand (RANKL)/receptor activator of nuclear factor κB (RANK) pathway, non-canonical Wnt/Ca2+/calmodulin dependent protein kinase II (CaMKII) pathway, and preventing of macrophage differentiation into osteoclasts, in addition, induction of apoptosis of osteoclasts through inhibiting farnesyl pyrophosphate synthase (FPPS)-mediated mevalonate pathway, and activation of reactive oxygen species (ROS)-induced pathway. Furthermore, ZA also inhibits cancer cells proliferation, viability, motility, invasion and angiogenesis; induces cancer cell apoptosis; reverts chemoresistance and stimulates immune response; and acts in synergy with other anti-cancer drugs. In addition, some new ways for delivering ZA against cancer is introduced. We hope this review will provide more information in support of future studies of ZA in the treatment of cancers and bone cancer metastasis.

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Section: Induction Of Apoptosis Of Osteoclastsmentioning

confidence: 99%

Section: Anticancer Effects Of Zamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review

Wang

Fang

et al. 2020

BMC Cancer

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“…OBP-301 enhances the sensitivity of osteosarcoma cells to the chemotherapeutic reagents doxorubicin and cisplatin [54]. Regarding the molecular mechanism underlying OBP-301's enhancement of chemosensitivity, adenoviral E1A protein upregulates the expression of E2F1 and microRNA-29, leading to suppression of the anti-apoptotic myeloid cell leukemia 1 protein [54,55]. Thus, the combination of OBP-301 and chemotherapy is a promising antitumor strategy for the treatment of osteosarcoma.…”

Section: Combination Therapy With Obp-301 and Chemotherapeutic Reagenmentioning

confidence: 99%

“…Zoledronic acid (ZOL) is a third-generation bisphosphonate that is used clinically for suppressing bone destruction in patients with metastatic bone tumors [59]. Combination therapy with OBP-301 and ZOL efficiently suppresses bone destruction caused by OBP-301-resistant osteosarcoma cells [55]. Moreover, Conry et al showed that ZOL treatment improves the progression-free survival in patients with metastatic osteosarcoma [60].…”

Section: Combination Therapy With Obp-301 and Chemotherapeutic Reagenmentioning

confidence: 99%

Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy

Tazawa

Hasei

Yano

et al. 2020

Cancers

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Adenovirus serotype 5 (Ad5) is widely and frequently used as a virus vector in cancer gene therapy and oncolytic virotherapy. Oncolytic virotherapy is a novel antitumor treatment for inducing lytic cell death in tumor cells without affecting normal cells. Based on the Ad5 genome, we have generated three types of telomerase-specific replication-competent oncolytic adenoviruses: OBP-301 (Telomelysin), green fluorescent protein (GFP)-expressing OBP-401 (TelomeScan), and tumor suppressor p53-armed OBP-702. These viruses drive the expression of the adenoviral E1A and E1B genes under the control of the hTERT (human telomerase reverse transcriptase-encoding gene) promoter, providing tumor-specific virus replication. This review focuses on the therapeutic potential of three hTERT promoter-driven oncolytic adenoviruses against bone and soft-tissue sarcoma cells with telomerase activity. OBP-301 induces the antitumor effect in monotherapy or combination therapy with chemotherapeutic drugs via induction of autophagy and apoptosis. OBP-401 enables visualization of sarcoma cells within normal tissues by serving as a tumor-specific labeling reagent for fluorescence-guided surgery via induction of GFP expression. OBP-702 exhibits a profound antitumor effect in OBP-301-resistant sarcoma cells via activation of the p53 signaling pathway. Taken together, telomerase-specific oncolytic adenoviruses are promising antitumor reagents that are expected to provide novel therapeutic options for the treatment of bone and soft-tissue sarcomas.

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Versatile Polymer‐Initiating Biomineralization for Tumor Blockade Therapy

et al. 2022

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dense extracellular matrix, prevent the cell-targeting therapeutic agents from penetrating deep into tumors and compromising their therapeutic effects. [1] As a fascinating non-cell-targeting strategy, the penetration-independent tumor blockade therapy obstructs the communications between the tumor and surrounding normal tissues by blocking tumor vasculature or building physical barriers. [2] Recently, vessel-targeted blockade therapy, including vascular disruption, arterial embolization, thrombosis induction, and so forth, [3] results in tumor malnutrition and accumulation of detrimental metabolites, ultimately leading to the ischemia and necrosis of central tumor region. [4] However, the viable marginal tumor tissue, cardiac ischemia, abnormal blood pressure, reversible neurologic complications, or other possible side effects have limited its clinical translation. [5] The construction of an artificial extracellular matrix (AECM) in the peripheral tumor tissue is another strategy for tumor blockade therapy. [6] AECM functions as an exogenous barrier and restrains the proliferation, migration, and invasion of cancer cells. For instance, Xu's group first reported fibrous nanonet formed by a small D-peptide derivative in the pericellular space. [7] The nanonets entrapped the secretory proteins and blocked cell Tumor blockade therapy is a promising penetration-independent antitumor modality, which effectively inhibits the exchange of nutrients, oxygen, and information between the tumor and surrounding microenvironments. However, the current blockade therapy strategies have limited antitumor efficacy due to defects of inadequate tumor obstruction, possible side effects, and short duration. For these reasons, a facilely synthesized versatile polymer 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)alendronate (DSPE-PEG-ALN, DPA) is developed to initiate the formation of biomineral shell around osteosarcoma as a potent physical barrier. The DSPE moiety shares a similar chemical structure with the cytomembrane, allowing the membrane insertion of DPA. The bisphosphonic acid groups in ALN attract ions to realize biomineralization around cells. After injection in the invasive osteosarcoma tissue, DPA inserts into the cytomembrane, induces continuous mineral deposition, and ultimately builds a physical barrier around the tumor. Meanwhile, ALN in DPA alleviates bone destruction by suppressing the activity of osteoclasts. Through hindering the exchange of necessary substances, the biomineralization coating inhibits the growth of primary osteosarcoma and pulmonary metastasis simultaneously. Therefore, the multifunctional polymer-initiating blockade therapy provides a promising modality for tumor inhibition in clinics with high efficacy and negligible side effects.

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Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction

Cited by 14 publications

References 46 publications

Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review

Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review

Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy

Versatile Polymer‐Initiating Biomineralization for Tumor Blockade Therapy

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