Exciting results in new study on bone-metastatic castration-resistant prostate cancer

Proud to present the results of our latest collaboration with Bayer AG and Aurexel Life Sciences! Our newest article, published in IJMS’s prostate cancer special issue Pathology, Pathobiology and Therapy, showed promising results for the treatment of bone-metastatic castration-resistant prostate cancer.

Pharmatest executed the in vivo experiments described in the article using the intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone.

The objective of this study was to evaluate the antitumor efficacy of combination treatment with radium-223 (Ra-223), and enzalutamide (Enza) on cancer growth and cancer-induced changes on bone. Combination treatment holds potential for improving the outcomes of patients with metastatic castration-resistant prostate cancer due to the distinctly different mechanisms of action supporting each other.

The results of our in vivo studies were very promising. The combination of Ra-223 and Enza showed synergistic antitumor efficacy as observed by lower PSA levels and smaller tumor-induced abnormal bone changes compared to monotherapies.

Also, the combination treatment was not observed to compromise bone architecture in the healthy tibiae. Radium-223 and enzalutamide combination treatment inhibited both bone formation (PINP) and bone resorption (CTX-I) in comparison to vehicle and enzalutamide monotherapies

The combination is currently under investigation in the clinical phase 3 PEACE III trial. The preclinical findings of our study support the clinical trial of this combination. 

Intratibial LNCaP Prostate Cancer model

Patients with prostate cancer frequently experience bone metastases. Bone metastases are present in nearly all patients with advanced prostate cancer. The main tumor might be effectively removed, but the illness may already have reached the bone. Prostate cancer-related bone metastases are primarily osteoblastic, resulting in the development of brittle bone and a significantly higher risk of fractures and bone pain. High bone resorption marker levels in prostate cancer patients with bone metastases show that bone resorption is higher even when the net effect is on the bone formation side.

The LNCaP prostate cancer cells are frequently used in preclinical research. The LNCaP cells are known to produce PSA, express PSMA and to cause mixed and osteoblastic lesions when inoculated into the bone marrow cavity. Using this model, it is possible to investigate how cancer drug candidates affect the growth of prostate cancer cells in bone.