Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
LINE-1 as a therapeutic target for castration-resistant prostate cancer
Prostate cancer is the third leading cause of death by cancer in men. Surgery or hormone deprivation usually contains the progression of the local forms of the disease. In metastatic situations, chemotherapy or second generation hormone therapies are used with an overall survival that never exceeds 36 months when tumors become resistant to castration. In the search for new alternatives, clinical trials with various classes of anticancer drugs have been performed, including chemotherapies, targeted therapies with kinase inhibitors, radium-223, or immunotherapies with somehow limited efficacy. Targeting LINE-1 with reverse transcriptase inhibitors was also proposed as an attractive strategy as retrotransposons may play a role in the initiation and the progression of prostate cancers. After reviewing the biological rational to use RT inhibitors in the treatment of prostate cancers, we will discuss the results of the phase II trial evaluating the efficacy of Efavirenz in the treatment of castration-resistant prostate cancers with a particular emphasis on pharmacokinetics data that were obtained. We will also discuss the positioning of other RT inhibitors in the current therapeutic armamentarium.