UNASSIGNED: Approximately up to 40% of @entity1 with @entity2 develop bone @entity3 , with 22% to 59% of them experiencing skeletal-related events (SREs), which result in an important quality of life deterioration and economic burden. Denosumab, a fully human antibody that targets the receptor activator of nuclear factor-kB (RANK) ligand ( @entity5298 ), is indicated for prevention of SREs in @entity1 with @entity5 and has demonstrated superiority in @entity0 , and in other @entity5 , in reducing the risk of first SRE by 17% versus @entity4381 . In the subset of @entity1 with @entity1149 ( @entity1149 ), denosumab has also shown a positive trend to SRE risk reduction. Denosumab might have direct or indirect antitumor effects. @entity5 cells produce factors that stimulate increased bone resorption by osteoclasts, which in turn release @entity5 growth factors into the bone microenvironment, initiating a @entity5 /bone vicious cycle. An increasing body of evidence suggests RANK/ @entity5298 signaling plays a role in this tumorigenesis. Both proteins are overexpressed in different @entity5 types including @entity2 cells. RANK/ @entity5298 signaling activates nuclear factor-kB pathways related to lung carcinogenesis and increases @entity2071 expression and @entity8047 /extracellular signal-regulated kinase phosphorylation, which in turn enhances @entity5 cell migration. In animal @entity1149 models, denosumab delayed bone @entity3 and reduced skeletal @entity5 growth. In @entity1 with @entity2 (post hoc analysis), denosumab prolonged overall survival by 1.2 months versus @entity4381 (P  = .01). This hypothesis-generating outcome warrants further investigation and 2 studies in @entity2 are ongoing to elucidate the therapeutic potential of denosumab beyond SRE prevention.

Therapeutic Potential of Denosumab in XXXX With @entity2 : Beyond Prevention of Skeletal Complications.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity8047 :: ('5609', 'Gene') :: ['MEK'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast and prostate cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Cancer', 'solid tumors'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung carcinoma'] @entity5298 :: ('8600', 'Gene') :: ['RANKL'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis', 'metastases'] @entity2071 :: ('3383', 'Gene') :: ['intercellular adhesion molecule 1'] @entity4381 :: ('MESH:C088658', 'Chemical') :: ['zoledronic acid']
@entity1 :: (9606,Species) :: ['Patients']
