New molecular targets in bone metastases.
Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future. Targeting the bone by preventing skeletal related events (SREs) and bone metastases has major clinical impact in improving survival in bone metastatic patients and in preventing disease relapse in adjuvant setting.
Medical Oncology Department, University Campus Bio-Medico, Via Alvaro del Portillo 200, Rome, Italy. d.santini@unicampus.it
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D
Santini
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S
Galluzzo
A
A
Zoccoli
F
F
Pantano
M E
ME
Fratto
B
B
Vincenzi
L
L
Lombardi
C
C
Gucciardino
N
N
Silvestris
E
E
Riva
S
S
Rizzo
A
A
Russo
E
E
Maiello
G
G
Colucci
G
G
Tonini
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D056657:Cathepsin K / Q000187:drug effects / Q000378:metabolism; D000069448:Denosumab; D016232:Endothelins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000187:drug effects / Q000378:metabolism; D053245:RANK Ligand / Q000187:drug effects / Q000378:metabolism / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D016232:Endothelins; D053245:RANK Ligand; D000069448:Denosumab; D016392:Proto-Oncogene Proteins pp60(c-src); D056657:Cathepsin K