The Role of RANK-Ligand Inhibition in Cancer: The Story of Denosumab

Abstract

The bone is a very common site of metastasis in patients with advanced cancer. Skeletal metastases are most common in breast and prostate cancer, but virtually any advanced cancer may disseminate to the bone. On the basis of recent advances in the understanding of bone remodeling processes, denosumab, a fully human monoclonal antibody against RANK-L, has been developed. Phase III clinical trials have demonstrated that denosumab is well tolerated and effective in the treatment of bone loss and prevention of skeletal-related events in patients with bone metastases.

Onco-Nephrology

“…Denosumab is a fully human monoclonal antibody that binds to RANKL and inhibits osteoclast maturation, activation, and function (85). It is FDA approved for preventing skeletal-related events in patients with solid malignancy, as well preventing bone fractures in postmenopausal women with osteoporosis.…”

“…It is FDA approved for preventing skeletal-related events in patients with solid malignancy, as well preventing bone fractures in postmenopausal women with osteoporosis. In clinical trials, denosumab has shown efficacy in preventing skeletal-related events (such as bone metastases) in patients with prostate, breast, and other solid-organ cancers, as well as multiple myeloma (85). Denosumab is well tolerated, with arthralgias as the most common side effect (86).…”

Skeletal-Related Events among Breast and Prostate Cancer Patients: Towards New Treatment Initiation in Malaysia's Hospital Setting

“…A pathologic fracture can result in impaired mobility or instability and spinal cord compression could cause severe pain, irreversible paraparesis, paraplegia or increased risk of death (Saad et al, 2007). These complications contribute to a decline in patients' health-related quality of life (HRQOL) (Castellano et al, 2011), including to the family of cancer patient (Bagi, 2005), costly (Schulman and Kohles, 2007;Hagiwara et al, 2011) and among men with metastatic prostate cancer, the skeletal-related events (SREs) were found to be associated with a decrease in survival (DePuy et al, 2007).…”

“…Neoplasm contributed 11.12% out of the ten principal causes of Hospital death in Ministry of Health, Malaysia in 2011(Ministry of Health, 2012. most common in breast, prostate and lung of primary solid tumour (Bagi, 2005;Castellano et al, 2011). Bone metastases become clinically importance in breast and prostate cancers partly contributed by the reason of prevalence of these diseases.…”

Neural Modulation of Orthodontic Tooth Movement

“…With the discovery of RANKL came efforts to utilize inhibitors of RANKL in the development of pharmaceutical agents that inhibit osteoclast activity. Recently an anti-RANKL antibody-based pharmaceutical (Denosumab) was generated by Amgen and approved as an anti-osteoporotic agent (Trade name Prolia) and for bone cancer (Xgeva) (Lewiecki, 2010;Castellano et al, 2011;Baron et al, 2011). Sclerostin has recently been identified as a vital regulator of bone formation (Moester et al, 2010).…”