Costello Leslie C, Franklin Renty B
Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, University of Maryland Greenebaum Comprehensive Cancer Center. Baltimore, Maryland, United States of America.
J Clin Res Oncol. 2019;2(1).
All cases of prostate cancer exhibit the hallmark condition of marked decrease in zinc in malignancy compared to the high zinc levels in the normal and benign prostate. There exists no reported corroborated case of prostate cancer in which malignancy exhibits the high zinc levels that exist in the normal prostate acinar epithelium. The decrease in zinc is achieved by the downregulation of ZIP1 zinc transporter, which prevents the uptake and accumulation of cytotoxic zinc levels. Thus, prostate cancer is a "ZIP1-deficient" malignancy. Testosterone and prolactin are the major hormones that similarly regulate the growth, proliferation, metabolism, and functional activities of the acinar epithelial cells in the peripheral zone (the site of development and progression of malignancy). Testosterone regulation provides the basis for androgen ablation treatment of advanced prostate cancer, which leads to the development of terminal androgen-independent malignancy. Androgen-independent malignancy progresses under the influence of prolactin. These relationships provide the basis for the prevention and treatment of advanced prostate cancer. Clioquinol (zinc ionophore; 5-chloro-7-iodoquinolin-8-ol) is employed to facilitate zinc transport and accumulation in the ZIP1-deficient malignant cells and induce cytotoxic effects. Cabergoline (dopamine agonist) is employed to decrease prolactin production and its role in the progression of androgen-independent malignancy. We propose a clioquinol/cabergoline treatment regimen that will be efficacious for aborting terminal advanced prostate cancer. FDA policies permit this treatment regimen to be employed for these patients.
与正常和良性前列腺中高锌水平相比，所有前列腺癌病例都表现出恶性肿瘤中锌显著减少的标志性情况。目前尚无报告证实存在前列腺癌病例，其中恶性肿瘤表现出正常前列腺腺泡上皮中存在的高锌水平。锌的减少是通过ZIP1锌转运体的下调实现的，这阻止了细胞毒性锌水平的摄取和积累。因此，前列腺癌是一种“ZIP1缺陷型”恶性肿瘤。睾酮和催乳素是主要激素，同样调节外周区腺泡上皮细胞的生长、增殖、代谢和功能活动（恶性肿瘤发生和进展的部位）。睾酮调节为晚期前列腺癌的雄激素剥夺治疗提供了基础，这会导致终末期雄激素非依赖性恶性肿瘤的发展。雄激素非依赖性恶性肿瘤在催乳素的影响下进展。这些关系为晚期前列腺癌的预防和治疗提供了基础。氯碘羟喹（锌离子载体；5-氯-7-碘喹啉-8-醇）用于促进锌在ZIP1缺陷型恶性细胞中的转运和积累，并诱导细胞毒性作用。卡麦角林（多巴胺激动剂）用于减少催乳素的产生及其在雄激素非依赖性恶性肿瘤进展中的作用。我们提出一种氯碘羟喹/卡麦角林治疗方案，该方案将对终止终末期晚期前列腺癌有效。美国食品药品监督管理局的政策允许将这种治疗方案用于这些患者。
