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使用氯喹或羟氯喹作为自噬抑制剂治疗癌症的临床价值:一项系统评价和荟萃分析

The clinical value of using chloroquine or hydroxychloroquine as autophagy inhibitors in the treatment of cancers: A systematic review and meta-analysis.

作者信息

Xu Ran, Ji Ziyi, Xu Chen, Zhu Jing

机构信息

Medical School of Nantong University.

Nanjing Normal University.

出版信息

Medicine (Baltimore). 2018 Nov;97(46):e12912. doi: 10.1097/MD.0000000000012912.

Abstract

BACKGROUND

Autophagy is a mechanism which relies on lysosomes for clearance and recycling of abnormal proteins or organelles. Many studies have demonstrated that the deregulation of autophagy is associated with the development of various diseases including cancer. The use of autophagy inhibitors is an emerging trend in cancer treatment. However, the value of autophagy inhibitors remains under debate. Thus, a meta-analysis was performed, aiming to evaluate the clinical value of autophagy-inhibitor-based therapy.

METHODS

We searched for clinical studies that evaluated autophagy-inhibitor-based therapy in cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR), 6-month progression-free survival (PFS) rate, and 1-year overall survival (OS) rate.

RESULTS

Seven clinical trials were identified (n = 293). Treatments included 2 combinations of hydroxychloroquine and gemcitabine, 1 combination of hydroxychloroquine and doxorubicin, 1 combination of chloroquine and radiation, 2 combinations of chloroquine, temozolomide, and radiation, and 1 hydroxychloroquine monotherapy. Autophagy-inhibitor-based therapy showed higher ORR (RR: 1.33, 95% confidence interval [CI]: 0.95-1.86, P = .009), PFS (RR: 1.72, 95% CI: 1.05-2.82, P = .000), OS (RR: 1.39, 95% CI: 1.11-1.75, P = .000) values than the therapy without inhibiting autophagy.

CONCLUSION

This meta-analysis showed that autophagy-inhibitor-based therapy has better treatment response compared to chemotherapy or radiation therapy without inhibiting autophagy, which may provide a new strategy for the treatment of cancers.

摘要

背景

自噬是一种依靠溶酶体清除和循环利用异常蛋白质或细胞器的机制。许多研究表明,自噬失调与包括癌症在内的各种疾病的发展有关。使用自噬抑制剂是癌症治疗中的一个新兴趋势。然而,自噬抑制剂的价值仍存在争议。因此,进行了一项荟萃分析,旨在评估基于自噬抑制剂的治疗的临床价值。

方法

我们检索了评估基于自噬抑制剂的癌症治疗的临床研究。我们从这些研究中提取数据,以评估总缓解率(ORR)、6个月无进展生存率(PFS)和1年总生存率(OS)的相对风险(RR)。

结果

确定了7项临床试验(n = 293)。治疗方法包括2种羟氯喹与吉西他滨的联合用药、1种羟氯喹与多柔比星的联合用药、1种氯喹与放疗的联合用药、2种氯喹、替莫唑胺与放疗的联合用药以及1种羟氯喹单药治疗。与未抑制自噬的治疗相比,基于自噬抑制剂的治疗显示出更高的ORR(RR:1.33,95%置信区间[CI]:0.95 - 1.86,P = 0.009)、PFS(RR:1.72,95%CI:1.05 - 2.82,P = 0.000)、OS(RR:1.39,95%CI:1.11 - 1.75,P = 0.000)值。

结论

这项荟萃分析表明,与未抑制自噬的化疗或放疗相比,基于自噬抑制剂的治疗具有更好的治疗反应,这可能为癌症治疗提供一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d93/6257684/af17f638cb88/medi-97-e12912-g002.jpg

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