Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review
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REVIEW
Open Access
Various pathways of zoledronic acid against osteoclasts and bone cancer metastasis: a brief review Lianwei Wang1†, Dengyang Fang1†, Jinming Xu1 and Runlan Luo2*
Abstract 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. Keywords: Zoledronic acid, Anticancer effect, Osteoclast, Bone cancer metastasis, Anti-resorptive drug
Background Osteoclasts, which are abundant in the bone tissue, are multinuclear cells derived from myeloid lineage [1, 2]. Osteoclasts are known to initiate physiologic bone remodeling during bone growth, tooth eruption and fracture healing, and also are able to mediate bone loss in pathologic conditions, such as bone cancer metastasis [3, 4]. Therefore, inhibition of osteoclasts is a potential target for the treatment of bone cancer metastasis. * Correspondence: [email protected] † Lianwei Wang and Dengyang Fang contributed equally to this work. 2 Department of Ultrasound, Fuling Central Hospital of Chongqing City, Chongqing 408300, China Full list of author information is available at the end of the article
According to the Global Cancer Statistics 2018, there would have 18.1 million new cancer cases and 9.6 million deaths from cancer worldwide in 2018 [5]. Increasing global demographic trends and epidemiologic transitions indicate an ever-increasing cancer burden over the coming decades, particularly in low- and middle-income countries, with over 20 million new cancer cases expected annually as early as 2025 [6]. The bone is the third most common site of metastasis for a wide range of solid tumors including lung, breast, prostate, colorectal, thyroid, gy
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