Gorski Justin W, Ueland Frederick R, Kolesar Jill M
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Kentucky Chandler Medical Center, 800 Rose Street, Lexington, KY 40536-0263, USA.
Department of Pharmacy Practice & Science, University of Kentucky College of Pharmacy, 567 TODD Building, 789 South Limestone Street, Lexington, KY 40539-0596, USA.
Diagnostics (Basel). 2020 May 5;10(5):279. doi: 10.3390/diagnostics10050279.
Ovarian cancer is the most-deadly gynecologic malignancy, with greater than 14,000 women expected to succumb to the disease this year in the United States alone. In the front-line setting, patients are treated with a platinum and taxane doublet. Although 40-60% of patients achieve complete clinical response to first-line chemotherapy, 25% are inherently platinum-resistant or refractory with a median overall survival of about one year. More than 80% of women afflicted with ovarian cancer will recur. Many attempts have been made to understand the mechanism of platinum and taxane based chemotherapy resistance. However, despite decades of research, few predictive markers of chemotherapy resistance have been identified. Here, we review the current understanding of one of the most common genetic alterations in epithelial ovarian cancer, CCNE1 (cyclin E1) amplification, and its role as a potential predictive marker of cytotoxic chemotherapy resistance. CCNE1 amplification has been identified as a primary oncogenic driver in a subset of high grade serous ovarian cancer that have an unmet clinical need. Understanding the interplay between cyclin E1 amplification and other common ovarian cancer genetic alterations provides the basis for chemotherapeutic resistance in CCNE1 amplified disease. Exploration of the effect of cyclin E1 amplification on the cellular machinery that causes dysregulated proliferation in cancer cells has allowed investigators to explore promising targeted therapies that provide the basis for emerging clinical trials.
卵巢癌是最致命的妇科恶性肿瘤，仅在美国，预计今年就有超过14000名女性会死于这种疾病。在一线治疗中，患者接受铂类和紫杉烷类双联化疗。尽管40%-60%的患者对一线化疗有完全的临床反应，但25%的患者天生对铂类耐药或难治，中位总生存期约为一年。超过80%的卵巢癌女性会复发。人们已经进行了许多尝试来了解基于铂类和紫杉烷类化疗耐药的机制。然而，尽管经过了数十年的研究，几乎没有发现化疗耐药的预测标志物。在这里，我们综述了目前对上皮性卵巢癌最常见的基因改变之一CCNE1（细胞周期蛋白E1）扩增的理解，及其作为细胞毒性化疗耐药潜在预测标志物的作用。CCNE1扩增已被确定为一部分有未满足临床需求的高级别浆液性卵巢癌的主要致癌驱动因素。了解细胞周期蛋白E1扩增与其他常见卵巢癌基因改变之间的相互作用，为CCNE1扩增疾病的化疗耐药提供了基础。对细胞周期蛋白E1扩增对导致癌细胞增殖失调的细胞机制的影响的探索，使研究人员能够探索有前景的靶向治疗方法，为正在进行的临床试验提供基础。
