Lack of AR Expression May Cause Prostate Cancer Treatment Resistance
Prostate cancer cells lacking androgen receptor (AR) expression do not respond to treatment and are more likely to grow, researchers reported in study findings published in Nature Communications (https://doi.org/10.1038/s41467-018-06067-7).
The researchers examined AR expression in 89 patients with castration-resistant prostate cancer and found three distinct patterns:
- AR in the nucleus of the cancer cell
- AR in the nucleus and cytoplasm
- Near or complete absence of AR from all parts of the cancer cell
They then discovered that patients with the last pattern did not respond to treatment with enzalutamide, and their prostate cancer cells were more likely to grow, regenerate, and proliferate. Finally, they identified BCL-2 as a critical regulator of this action and an important therapeutic target and found new evidence suggesting that combining enzalutamide with ABT-199, a newly approved BCL-2 inhibitor, may increase response in castration-resistant prostate cancer.
Phase Ib/II clinical trials are underway to confirm the results.