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Endometrial Carcinoma: A Review of Chemotherapy, Drug Resistance, and the Search for New Agents

机译:子宫内膜癌:化疗,耐药性和寻找新的药物的审查。

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Adenocarcinoma of the endometrium represents the most common gynecologic malignancy in developed countries. Although early-stage cancers are effectively treated surgically, commonly without adjuvant therapy, the treatment of high-risk and advanced disease is more complex. Chemotherapy has evolved into an important modality in high-risk early-stage and advanced-stage disease, and in recurrent endometrial cancer. Taxane-based therapy consistently demonstrates the highest response rates in the first-line and salvage settings of endometrial cancer. Unfortunately, response to chemotherapy is modest and strategies are needed to predict chemotherapy-responsive and chemotherapy-resistant populations. Chemotherapy resistance mediated by overexpression of drug efflux pump proteins and mutations in β-tubulin isoforms in both primary and recurrent disease represent unique treatment challenges and highlight the need for new agents that are less susceptible to these known resistance pathways. Epothilone B analogs are novel cytotoxic agents with activity in solid tumors, including advanced/recurrent endometrial carcinoma, and may have unique properties that can overcome resistance in some settings. These agents alone and in combination represent a new therapeutic opportunity in endometrial carcinoma.
机译:子宫内膜腺癌是发达国家中最常见的妇科恶性肿瘤。尽管可以通过手术有效地治疗早期癌症(通常无需辅助治疗),但高危和晚期疾病的治疗更为复杂。在高危早期和晚期疾病以及复发性子宫内膜癌中,化学治疗已发展成为一种重要的治疗方式。基于紫杉烷的疗法在子宫内膜癌的一线和挽救环境中始终显示出最高的响应率。不幸的是,对化学疗法的反应是中等的,并且需要策略来预测对化学疗法有响应和对化学疗法有抵抗力的人群。在原发性和复发性疾病中,由药物外排泵蛋白的过表达和β-微管蛋白亚型的突变介导的化疗耐药性代表着独特的治疗挑战,并突出了对新药的需求,这些新药对这些已知的耐药性途径较不敏感。埃博霉素B类似物是在实体瘤(包括晚期/复发性子宫内膜癌)中具有活性的新型细胞毒性剂,并且可能具有在某些情况下可以克服耐药性的独特特性。这些试剂单独或组合代表子宫内膜癌的新治疗机会。

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