Recent advances in bone-targeted therapies of metastatic prostate cancer.
Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved.
College of Medicine, Hunan Normal University, Changsha, Hunan 410013, China; Changsha Microworld Biotech Company, Changsha, Hunan 410004, China.
Xiyun
X
Deng
College of Medicine, Hunan Normal University, Changsha, Hunan 410013, China.
Guangchun
G
He
National Engineering Laboratory for Rice and Byproduct In-Depth Processing, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.
Junwen
J
Liu
National Engineering Laboratory for Rice and Byproduct In-Depth Processing, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.
Feijun
F
Luo
College of Medicine, Hunan Normal University, Changsha, Hunan 410013, China.
Xiaoning
X
Peng
College of Medicine, Hunan Normal University, Changsha, Hunan 410013, China.
Shigang
S
Tang
College of Medicine, Hunan Normal University, Changsha, Hunan 410013, China.
Zhiyong
Z
Gao
National Engineering Laboratory for Rice and Byproduct In-Depth Processing, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.
Qinlu
Q
Lin
Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA.
Jill M
JM
Keller
National Engineering Laboratory for Rice and Byproduct In-Depth Processing, Central South University of Forestry and Technology, Changsha, Hunan 410004, China; Changsha Microworld Biotech Company, Changsha, Hunan 410004, China. Electronic address: yangtao807@163.com.
Tao
T
Yang
Department of Urology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: etkeller@umich.edu.
Evan T
ET
Keller
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001862:Bone Resorption / Q000188:drug therapy / Q000517:prevention & control*; D056657:Cathepsin K / Q000187:drug effects / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D010012:Osteogenesis / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology*; D053245:RANK Ligand / Q000187:drug effects* / Q000378:metabolism; D011868:Radioisotopes / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D053245:RANK Ligand; D011868:Radioisotopes; C505688:TNFSF11 protein, human; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D056657:Cathepsin K
Bone metastasis; Molecular targeted therapy; Osteoblasts; Osteoclasts; Prostate cancer; RANKL