Can focused ultrasound sensitize androgen-independent prostate cancer cells to antiandrogen therapy?

Antiandrogen therapy, such as Enzalutamide (Enz), is used for the treatment of prostate cancer. Enz works as antagonist of the androgen receptor (AR) preventing or reducing the binding of the hormones such as testosterone and dihydrotestosterone in the prostate gland and elsewhere in the body. This inhibits cancer progression and induces cancer cell death. However, Enz and other antiandrogens are only effective for a period of time, after which prostate cancer cells develop resistance to this medication. A 22Rv1 cell line is a model for this resistant, androgen-independent prostate cancer, in which native AR is replaced with AR splice variants that do not contain binding sites for hormones or antiandrogens. The AR splice variants cause AR activation without ligation, leading to uncontrollable cell growth even under exposure to antiandrogen medication. In this work, we show that the mechanical disruption of the cytoskeleton and nuclear chromatin by focused ultrasound resets AR in 22Rv1 cells, thus stopping cancer cell growth and breaking their resistance to Enz.