Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.
Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.
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晚期卵巢癌是妇科死亡的主要原因，其复发率很高，表明迫切需要改进治疗方法。卵巢癌的热腹腔化疗 (HIPEC) 治疗已显示出延长患者总生存期的功效，但其获益机制仍不清楚。本次综述的目的是解决高热的影响，提供对 HIPEC 疗效的见解。在这里，我们回顾了 HIPEC 治疗卵巢癌和腹膜癌的报告，以及用于模拟临床 HIPEC 的动物模型的讨论。上皮性卵巢癌是女性生殖系统的一种侵袭性疾病，也是女性癌症死亡的主要原因。标准护理包括手术和铂类化疗，但患者的复发和转移率仍然很高。高选择性患者的腹腔热腹化疗 (HIPEC) 治疗可将总生存期延长近 12 个月。临床研究高度支持使用 HIPEC 治疗卵巢癌，尽管这种治疗方法仅限于学术医疗中心。 HIPEC 益处的机制仍不清楚。 HIPEC 治疗的疗效受到多种手术和患者/肿瘤因素的影响，包括手术时机、铂类敏感性和分子分析（例如同源重组缺陷）。本综述旨在深入了解 HIPEC 治疗的机制益处，重点关注热疗如何激活免疫反应、诱导 DNA 损伤、损害 DNA 损伤修复途径，并与化疗产生协同效应，最终结果是增加化疗敏感性。确定 HIPEC 揭示的脆弱点可能会提供关键途径，从而成为卵巢癌患者新治疗策略的基础。
Advanced ovarian cancer is the leading cause of gynecological death with a high rate of reoccurrence indicating the critical need for improved therapeutics. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment for ovarian cancer has shown efficacy in extending patient overall survival yet the mechanism of benefit remains unknown. The aim of this review is to address the impact of hyperthermia, providing insights into HIPEC efficacy. Here we review reports of HIPEC treatment in ovarian and peritoneal cancers as well as discussion of animal models used for emulating clinical HIPEC. Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy, yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer, though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage, impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients.
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影响因子：
4
作者：
Brenu EW;Staines DR;Tajouri L;Huth T;Ashton KJ;Marshall-Gradisnik SM
通讯作者：
Marshall-Gradisnik SM
影响因子：
3.8
作者：
Bakrin, N.;Bereder, J. M.;Glehen, O.
通讯作者：
Glehen, O.
影响因子：
2.2
作者：
Foulkes, William D.
通讯作者：
Foulkes, William D.
DOI：
10.1038/s41577-021-00524-z
发表时间：
2021-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Decout A;Katz JD;Venkatraman S;Ablasser A
通讯作者：
Ablasser A
影响因子：
--
作者：
Chen A
通讯作者：
Chen A