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用于持续性或复发性子宫颈癌的放射性药物。

Radiopharmaceuticals for Persistent or Recurrent Uterine Cervix Cancer.

作者信息

Kunos Charles A, Capala Jacek, Kohn Elise C, Ivy Susan Percy

机构信息

Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, United States.

Radiation Research Program, National Cancer Institute, Bethesda, MD, United States.

出版信息

Front Oncol. 2019 Jun 26;9:560. doi: 10.3389/fonc.2019.00560. eCollection 2019.

Abstract

Uterine cervix cancers pose therapeutic challenges because of an overactive ribonucleotide reductase, which provides on-demand deoxyribonucleotides for DNA replication or for a DNA damage repair response. Ribonucleotide reductase overactivity bestows cancer cell resistance to the effects of radiotherapy and chemotherapy used to treat disease; but nevertheless, this same biologic overexpression provides opportune vulnerabilities relatively specific to uterine cervix cancers for new therapeutic strategies to take advantage. The discovery of human epidermal growth factor receptor 2 ( or HER2) overexpression on metastatic uterine cervix cancer cells provides an opportunity for clinical trials of targeted radiopharmaceuticals in combination with DNA damage response modifying drugs. The National Cancer Institute's clinical trial infrastructure and its experimental therapeutics portfolio can now offer clinical trial evaluation of molecularly-targeted and tolerated radiopharmaceutical-drug combinations for women with persistent or recurrent metastatic uterine cervix cancer. This article discusses the current thinking of the National Cancer Institute in regard to attractive radiopharmaceutical strategies for this disease and others.

摘要

子宫颈癌因其核糖核苷酸还原酶过度活跃而带来治疗挑战,该酶可为DNA复制或DNA损伤修复反应按需提供脱氧核糖核苷酸。核糖核苷酸还原酶过度活跃赋予癌细胞对用于治疗疾病的放疗和化疗的抗性;然而,这种相同的生物学过表达为子宫颈癌相对特有的新治疗策略提供了合适的脆弱点以供利用。在转移性子宫颈癌细胞上发现人表皮生长因子受体2(HER2)过表达,为靶向放射性药物与DNA损伤反应修饰药物联合进行临床试验提供了机会。美国国立癌症研究所的临床试验基础设施及其实验性治疗产品组合,现在可以为患有持续性或复发性转移性子宫颈癌的女性提供分子靶向且耐受性良好的放射性药物 - 药物组合的临床试验评估。本文讨论了美国国立癌症研究所目前对于该疾病及其他疾病有吸引力的放射性药物策略的看法。

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