Antimetastatic Effects of a Novel Telomerase Inhibitor, GRN163L, on Human Prostate Cancer

摘要

Prostate adenocarcinoma is the most common type of cancer found in men, being second to lung cancer in terms of morbidity. While there are several therapeutic options (surgery, radiation) for the patients with localized disease, the patients with metastatic disease have only a few therapeutic options, all with limited efficacy. Therefore it is important to developed and implement new chemotherapeutic drugs for the treatment of prostate cancer. One of these novel therapeutic agents is imetelstat sodium (GRN163L), an oligonucleotide antagonist which targets the telomerase. Re-activation of telomerase, the enzyme responsible for maintenance of telomeres, is one of the hallmarks of cancer and more than 90% of prostate carcinomas possess this phenotype. In the absence of telomerase, cancer cells will progressively shorten their telomeres to a critical length and die. The majority of conventional chemotherapies are believed to leave intact small population of cells, known as tumor-initiating cells (or cancer stem cells). These cells are believed to be responsible for the subsequent relapse and metastasis of the disease and specific therapies which target these cells may achieve a more durable response. If tumorinitiating cells have telomerase activity, the imetelstat drug would target these cells in addition to the bulk tumor cells. In this study we are assessing the anti-metastatic effects of imetelstat by demonstrating that this drug targets the rare populations of tumorinitiating cells by inducing telomerase inhibition and telomere shortening.