RANKL inhibition is an effective adjuvant for docetaxel in a prostate cancer bone metastases model.
BACKGROUND
Docetaxel induces an anti-tumor response in men with advanced prostate cancer (PCa); however, the side effects associated with docetaxel treatment can be severe, resulting in discontinuation of therapy. Thus, identification of an effective adjuvant therapy to allow lower doses of docetaxel is needed. Advanced PCa is typically accompanied by skeletal metastasis. Receptor activator of NFkB ligand (RANKL) is a key pro-osteoclastic factor. Targeting RANKL decreases establishment and progression of PCa growth in bone in murine models.


METHODS
The efficacy of inhibiting RANKL, using a recombinant soluble RANK extracellular domain fused with the immunoglobulin Fc domain (RANK-Fc), was tested as an adjuvant therapy with docetaxel for PCa bone metastasis in a murine intra-tibial model.


RESULTS
The combination of RANK-Fc and docetaxel reduced tumor burden in bone greater than either treatment alone.


CONCLUSIONS
The combination of docetaxel with a RANKL-inhibiting agent merits further investigation for treatment of advance PCa.
Ignatoski
K M Woods
KM
Department of Urology, University of Michigan Health Systems, Ann Arbor, Michigan 48109-0940, USA.
Escara-Wilke
J F
JF
Dai
J-L
JL
Lui
A
A
Dougall
W
W
Daignault
S
S
Yao
Z
Z
Zhang
J
J
Day
M L
ML
Sargent
E E
EE
Keller
E T
ET
D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D011859:Radiography; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
D000277:Adjuvants, Pharmaceutic; D053245:RANK Ligand; C517736:Rank-Fc; D011993:Recombinant Fusion Proteins; D043823:Taxoids; D000077143:Docetaxel