New study assessing bone health effects of radium-223, abiraterone acetate, prednisone, and zoledronic acid combo treatment in prostate cancer bone metastases model, revealing potential fracture risk mechanisms.
Pharmatest had the pleasure to collaborate in performing this recent study, where the bone health effects of radium-223, abiraterone acetate, prednisone, and zoledronic acid combo treatment were assessed.
During phase 2 clinical trials, it was noted that patients with bone metastatic castration-resistant prostate cancer (CRPC) receiving radium-223 combo treatment experienced a heightened risk of fractures. However, simultaneous administration of bone-protecting agents reduced the occurrence of fractures.
The object of this preclinical study was to reveal the mechanisms behind the increased risk of fractures using Pharmatest’s intratibial LNCaP prostate cancer xenograft model. This metastasis model mimics the tumor-induced changes in bone that are common in metastatic prostate cancer.
Results show that the combination treatment led to a temporary rise in bone resorption, but concurrent zoledronic acid treatment suppressed this effect. The combination also reduced new bone formation and osteoblast count without affecting bone structure or quality. Interestingly, the treatment hindered radium-223 incorporation into tumor-bearing bone. The findings suggest that the combination treatment raised bone resorption, potentially contributing to the heightened fracture risk in patients with metastatic castration-resistant prostate cancer (mCRPC).
Radium-223 is currently being studied in phase 3 study PEACE III (EORTC‑333‑GUCG)
Xenograft Mouse Models
Xenograft mouse models are widely used for evaluating the in vivo effectiveness of novel anti-cancer drug candidates. Growing xenografts in sites relevant to the disease progression further enhances the effectiveness.
Mouse xenografts models involve the transplantation of human cancer cell-lines into immunodeficient or humanized mice. Therefore, xenograft models can capture the heterogeneity of human tumors, including genetic and molecular variations making them valuable to understanding different aspects of cancer biology. These models are useful for studying also cancer metastasis, which is crucial for development of treatments to prevent and treat metastatic cancers.