Radiopotentiation of enzalutamide over human prostate cancer cells as assessed by real-time cell monitoring

Abstract

Aim: To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells. Background: While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. Materials and methods: Here, we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real-time cell analysis (RTCA), androgen-sensitive LNCaP cells (Lymph Node Carcinoma of the Prostate) and androgenindependent PC-3. Both cell lines were highly resistant to high doses of radiotherapy. Results: A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. Conclusions: These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.

Systematic Multi-Omics Investigation of Androgen Receptor Driven Gene Expression and Epigenetics changes in Prostate Cancer

“…Additionally, treating LNCaP cells with enzalutamide sensitized them to radiotherapy, enhanced apoptosis, delayed DNA repair, and decreased colony survival 27,28 .…”

Phase II Study of ENZAlutamide Combined With Hypofractionated Radiation Therapy (ENZART) for Localized Intermediate Risk Prostate Cancer

“…Enzalutamide monotherapy radiosensitizes prostate cancer cells to radiation ( 29 ) by inducing the suppression of DNA repair mechanisms, mainly through non-homologous end-joining repair suppression mediated by DNAPKc proteins ( 30 ). This sensitizing effect was also demonstrated in androgen-sensitive and resistant prostate cancer cell lines, animal models, and xenografts on castration-resistant human prostate cancers ( 31 ).…”

“…This sensitizing effect was also demonstrated in androgen-sensitive and resistant prostate cancer cell lines, animal models, and xenografts on castration-resistant human prostate cancers ( 31 ). Enzalutamide provides a stronger radiosensitation than ADT ( 32 ) and, furthermore, this effect is more relevant when higher than 2 Gy doses per fraction ( 29 ) are used and enzalutamide is administered concurrently with RT ( 31 ). This improved effect on concomitant-adjuvant hormonal therapy with radiotherapy has also been observed for standard ADT in the clinical setting ( 33 ).…”