Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression.
These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI. Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.
Written by:
Iuliani M, Pantano F, Buttigliero C, Fioramonti M, Bertaglia V, Vincenzi B, Zoccoli A, Ribelli G, Tucci M, Vignani F, Berruti A, Scagliotti GV, Tonini G1, Santini D. Are you the author?
Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy; Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy; U.O. Oncologia Medica, Ospedali Civili di Brescia, Brescia, Italy.
Reference: Oncotarget. 2015 Mar 30. Epub ahead of print.
PubMed Abstract
PMID: 25904051