[Molecular basis of bone metastasis formation and its targeted therapy].
Formation of bone metastasis is a hallmark of the progression of several solid cancers, providing example for the organ specificity of the process. Bone metastasis may result in both venous and arterial dissemination. Though the molecular basis of the lytic and plastic bone metastasis formation is different, in reality these organ metastases represent a mixture of the two processes. The basis of bone metastasis formation is the activation of osteoclasts and the resulting bone resorption, initiating a vicious circle by activating the initiator cancer cell. The discovery of osteoclast-bone matrix interaction inhibitor bisphosphonates revolutionized the therapy of bone metastasis. Clarifying the molecular pathways involved in bone metastasis formation identified osteoclast differentiation as another feasible target. This process is under control of the TNF receptor family member RANK and its ligand RANKL. The feasibility of using this system to control bone resorption or cancer-induced skeletal events was proven clinically in trials using an anti-RANKL antibody. The clinical success of anti-RANKL antibody therapy provide further evidence that only precise identification of molecular pathways operational in cancers can lead to discovery of more effective (targeted) therapies.
Tímár
József
J
Semmelweis Egyetem, II. sz. Patológiai Intézet, 1091 Budapest, Ulloi út 93. jtimar@korb2.sote.hu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000556:secondary; D001862:Bone Resorption / Q000188:drug therapy*; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053245:RANK Ligand; D018124:Receptors, Tumor Necrosis Factor