Zoledronic Acid: Pleiotropic Anti-tumor Mechanism and Therapeutic Outlook for Osteosarcoma

Zhengxiao Ouyang, Haowei Li, Zanjing Zhai, Jiake Xu, Crispin R. Dass, An Qin, Kerong Dai

Research output: Contribution to journalReview article

Abstract

Background: Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce osteolysis induced by bone metastasis and exhibit highly selective localization and retention in bone, thus making them attractive agents in the treatment of bone metastasis. Studies have shown that zoledronic acid exerts pleiotropic anti-tumor effects against osteosarcoma cells in vitro, including anti-proliferative, anti-angiogenic, and immunomodulatory effects. However, the efficacy of zoledronic acid against primary tumor growth and pulmonary metastasis of osteosarcoma is controversial, which has limited its clinical application.

Objective: The present review summarizes the controversial effects of zoledronic acid on primary tumor burden and pulmonary metastases in osteosarcoma. We also analyze the clinical effectiveness of zoledronic acid alone and in combination with chemotherapeutic drugs for the treatment of osteosarcoma.

Conclusion: Zoledronic acid exhibits diverse anti-tumor effects in osteosarcoma in vitro, however, the in vivo effect is still controversial. Further preclinical and clinical studies are needed to clarify the effects of zoledronic acid in osteosarcoma.

Original languageEnglish
Pages (from-to)409-421
Number of pages13
JournalCurrent Drug Targets
Volume19
Issue number5
DOIs
Publication statusPublished - 2018

Cite this

Ouyang, Zhengxiao ; Li, Haowei ; Zhai, Zanjing ; Xu, Jiake ; Dass, Crispin R. ; Qin, An ; Dai, Kerong. / Zoledronic Acid : Pleiotropic Anti-tumor Mechanism and Therapeutic Outlook for Osteosarcoma. In: Current Drug Targets. 2018 ; Vol. 19, No. 5. pp. 409-421.
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abstract = "Background: Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce osteolysis induced by bone metastasis and exhibit highly selective localization and retention in bone, thus making them attractive agents in the treatment of bone metastasis. Studies have shown that zoledronic acid exerts pleiotropic anti-tumor effects against osteosarcoma cells in vitro, including anti-proliferative, anti-angiogenic, and immunomodulatory effects. However, the efficacy of zoledronic acid against primary tumor growth and pulmonary metastasis of osteosarcoma is controversial, which has limited its clinical application.Objective: The present review summarizes the controversial effects of zoledronic acid on primary tumor burden and pulmonary metastases in osteosarcoma. We also analyze the clinical effectiveness of zoledronic acid alone and in combination with chemotherapeutic drugs for the treatment of osteosarcoma.Conclusion: Zoledronic acid exhibits diverse anti-tumor effects in osteosarcoma in vitro, however, the in vivo effect is still controversial. Further preclinical and clinical studies are needed to clarify the effects of zoledronic acid in osteosarcoma.",
keywords = "Bisphosphonate, osteolysis, osteosarcoma, pulmonary metastasis, zoledronic acid, bone, DELTA-T-CELLS, DIAGNOSED METASTATIC OSTEOSARCOMA, ENDOTHELIAL GROWTH-FACTOR, BREAST-CANCER CELLS, IN-VITRO, 3RD-GENERATION BISPHOSPHONATE, MURINE OSTEOSARCOMA, BONE METASTASES, PHASE-II, PROGNOSTIC-SIGNIFICANCE",
author = "Zhengxiao Ouyang and Haowei Li and Zanjing Zhai and Jiake Xu and Dass, {Crispin R.} and An Qin and Kerong Dai",
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Zoledronic Acid : Pleiotropic Anti-tumor Mechanism and Therapeutic Outlook for Osteosarcoma. / Ouyang, Zhengxiao; Li, Haowei; Zhai, Zanjing; Xu, Jiake; Dass, Crispin R.; Qin, An; Dai, Kerong.

In: Current Drug Targets, Vol. 19, No. 5, 2018, p. 409-421.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Zoledronic Acid

T2 - Pleiotropic Anti-tumor Mechanism and Therapeutic Outlook for Osteosarcoma

AU - Ouyang, Zhengxiao

AU - Li, Haowei

AU - Zhai, Zanjing

AU - Xu, Jiake

AU - Dass, Crispin R.

AU - Qin, An

AU - Dai, Kerong

PY - 2018

Y1 - 2018

N2 - Background: Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce osteolysis induced by bone metastasis and exhibit highly selective localization and retention in bone, thus making them attractive agents in the treatment of bone metastasis. Studies have shown that zoledronic acid exerts pleiotropic anti-tumor effects against osteosarcoma cells in vitro, including anti-proliferative, anti-angiogenic, and immunomodulatory effects. However, the efficacy of zoledronic acid against primary tumor growth and pulmonary metastasis of osteosarcoma is controversial, which has limited its clinical application.Objective: The present review summarizes the controversial effects of zoledronic acid on primary tumor burden and pulmonary metastases in osteosarcoma. We also analyze the clinical effectiveness of zoledronic acid alone and in combination with chemotherapeutic drugs for the treatment of osteosarcoma.Conclusion: Zoledronic acid exhibits diverse anti-tumor effects in osteosarcoma in vitro, however, the in vivo effect is still controversial. Further preclinical and clinical studies are needed to clarify the effects of zoledronic acid in osteosarcoma.

AB - Background: Osteosarcoma is considered the most frequent primary bone malignancy. Lung metastasis is the leading cause of death and the most consistent factor for predicting negative patient outcome in osteosarcoma. Third-generation nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to reduce osteolysis induced by bone metastasis and exhibit highly selective localization and retention in bone, thus making them attractive agents in the treatment of bone metastasis. Studies have shown that zoledronic acid exerts pleiotropic anti-tumor effects against osteosarcoma cells in vitro, including anti-proliferative, anti-angiogenic, and immunomodulatory effects. However, the efficacy of zoledronic acid against primary tumor growth and pulmonary metastasis of osteosarcoma is controversial, which has limited its clinical application.Objective: The present review summarizes the controversial effects of zoledronic acid on primary tumor burden and pulmonary metastases in osteosarcoma. We also analyze the clinical effectiveness of zoledronic acid alone and in combination with chemotherapeutic drugs for the treatment of osteosarcoma.Conclusion: Zoledronic acid exhibits diverse anti-tumor effects in osteosarcoma in vitro, however, the in vivo effect is still controversial. Further preclinical and clinical studies are needed to clarify the effects of zoledronic acid in osteosarcoma.

KW - Bisphosphonate

KW - osteolysis

KW - osteosarcoma

KW - pulmonary metastasis

KW - zoledronic acid

KW - bone

KW - DELTA-T-CELLS

KW - DIAGNOSED METASTATIC OSTEOSARCOMA

KW - ENDOTHELIAL GROWTH-FACTOR

KW - BREAST-CANCER CELLS

KW - IN-VITRO

KW - 3RD-GENERATION BISPHOSPHONATE

KW - MURINE OSTEOSARCOMA

KW - BONE METASTASES

KW - PHASE-II

KW - PROGNOSTIC-SIGNIFICANCE

U2 - 10.2174/1573399811666150615145409

DO - 10.2174/1573399811666150615145409

M3 - Review article

VL - 19

SP - 409

EP - 421

JO - Current Drug Targets

JF - Current Drug Targets

SN - 1389-4501

IS - 5

ER -