Abstract
87 ISSN 1758-1966 10.2217/LMT.12.16 © 2012 Future Medicine Ltd Lung Cancer Manage. (2012) 1(2), 87–90 Patients with metastatic bone disease may suffer from skeletal-related events (SREs) such as fractures, pain requiring radiation or bone surgery, spinal cord compression or hypercalcemia, severely affecting their quality of life as well as generating significant hospital and financial costs. Notably, approximately 30–50% of patients suffering from lung cancer develop bone metastases at some point or have bone involvement at the time of diagnosis. These patients are known to present with a high frequency of SREs comparable to other solid tumors often metastasizing to bone, such as breast and prostate cancers [1,2]. The occurrence of non-small-cell lung cancer (NSCLC) SREs was shown to predict an unexpectedly short life expectancy for these patients [3]. Zoledronic acid acts on bone metabolism by disrupting the HMG-CoA reductase pathway and blocking osteoclastogenesis, as well as osteoclast cytoskeletal arrangement. It is frequently administered as part of the overall management of patients with bone metastases and was demonstrated to be effective compared with placebo in prolonging time to first SRE in patients with bone metastases [1,2,4]. Recently, targeting the OPG/RANKL/ RANK pathway was revealed to be an interesting strategy in patients suffering from virtually all bone metastatic advanced solid tumors [5–7]. The RANK pathway plays a major role in osteoclast function and therefore contributes to the subtle regulation of bone turnover. RANK is a member of the TNFR superfamily. RANK and OPG are both receptors for RANKL. However, whereas RANK signaling is stimulated upon RANKL binding, OPG is a secreted decoy receptor that acts as a natural inhibitor of the pathway [8]. Biologically, RANKL is a potent osteoclastogenic factor expressed on osteoblasts and osteocytes, promoting survival, proliferation, differentiation and activation of mature osteoclasts. While the RANK pathway is specifically involved in bone homeostasis, its deregulation was shown to be one of the initiators of SREs in cancer [9]. Apart from bone matrix cells, the transmembrane RANK protein is strongly expressed on lymphocytes, dendritic cells,
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call