Medical Oncology Department, Nimes University Hospital, Nimes, France, INSERM U1194, Montpellier Cancer Research Institute, and Montpellier University, France.
INSERM U1215, Physiopathology of Neuronal Plasticity, Neurocentre Magendie and Bordeaux University, France.
Front Biosci (Landmark Ed). 2018 Jan 1;23(7):1292-1309. doi: 10.2741/4644.
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.
前列腺癌是男性癌症死亡的第三大主要原因。手术或激素剥夺通常可控制局部疾病的进展。在转移性情况下，使用化疗或第二代激素疗法，当肿瘤对去势产生耐药性时，总生存期从未超过 36 个月。为了寻找新的替代方法，已经进行了各种类别的抗癌药物的临床试验，包括化疗、具有激酶抑制剂的靶向治疗、镭-223 或免疫疗法，但疗效有限。用逆转录酶抑制剂靶向 LINE-1 也被提出作为一种有吸引力的策略，因为反转录转座子可能在前列腺癌的发生和进展中发挥作用。在回顾了使用逆转录酶抑制剂治疗前列腺癌的生物学合理性之后，我们将讨论评估 Efavirenz 治疗去势抵抗性前列腺癌的 II 期临床试验结果，特别强调了所获得的药代动力学数据。我们还将讨论其他逆转录酶抑制剂在当前治疗武器库中的定位。
