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纳曲酮对癌症进展和死亡率的影响:人类、动物模型和细胞培养研究的系统评价。

Naltrexone's Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures.

机构信息

Schulich School of Medicine, Western University, London, ON, Canada.

Bloor Pain Specialists, Toronto, ON, Canada.

出版信息

Adv Ther. 2021 Feb;38(2):904-924. doi: 10.1007/s12325-020-01591-9. Epub 2020 Dec 18.

DOI:10.1007/s12325-020-01591-9
PMID:33337537
Abstract

BACKGROUND

Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN.

METHODS

A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies.

RESULTS

Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3-5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy.

CONCLUSION

This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy.

摘要

背景

纳曲酮(NTX)是一种阿片类拮抗剂,传统上用于治疗酒精和阿片类药物使用障碍,但各种研究都记录了它在癌症进展中的作用,探索了高剂量或低剂量纳曲酮(LDN)给药时的潜在抗癌作用。本文系统回顾了使用细胞培养物、动物模型和接受 NTX/LDN 的人类受试者进行的病例报告、临床试验以及回顾性和前瞻性研究中与癌症相关的结果。

方法

对 NTX 在癌症治疗中的应用进行了系统搜索。在临床和动物研究中,评估了包括肿瘤大小和数量、肿瘤发展潜伏期、生存时间、疾病进展和扫描结果在内的结果,在培养研究中,细胞数量用作结果衡量指标。

结果

几项病例报告表明,晚期癌症患者接受平均 3-5mg/天的 LDN 剂量治疗后,存活时间和转移性缓解显著。动物和细胞培养研究表明,NTX 参与癌症药理生理学的一个总体原则是,高剂量和连续给药可能促进癌症进展,而低剂量和间歇性治疗可能会抑制细胞增殖、阻碍肿瘤发生,并具有潜在的抗癌功效。

结论

本文强调了未来在癌症治疗中研究 NTX 的价值,并需要更好地了解其潜在机制。需要进行更多具有更大样本量的对照研究,特别是在人类中,以充分阐明其在癌症治疗中的潜力。

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本文引用的文献

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Low Dose Naltrexone and Lung Cancer: A Case Report and Discussion.低剂量纳曲酮与肺癌:一例报告及讨论
Cureus. 2018 Jul 5;10(7):e2924. doi: 10.7759/cureus.2924.
2
Low-dose naltrexone (LDN): A promising treatment in immune-related diseases and cancer therapy.低剂量纳曲酮(LDN):免疫相关疾病和癌症治疗中具有广阔前景的一种治疗方法。
Int Immunopharmacol. 2018 Aug;61:178-184. doi: 10.1016/j.intimp.2018.05.020. Epub 2018 Jun 7.
3
The Long-Term Survival of a Patient With Stage IV Renal Cell Carcinoma Following an Integrative Treatment Approach Including the Intravenous α-Lipoic Acid/Low-Dose Naltrexone Protocol.
阿片受体μ拮抗剂在癌症患者中的应用:事实还是虚构?
Curr Oncol Rep. 2022 Oct;24(10):1337-1349. doi: 10.1007/s11912-022-01295-z. Epub 2022 Jun 1.
一名IV期肾细胞癌患者采用包括静脉注射α-硫辛酸/低剂量纳曲酮方案在内的综合治疗方法后的长期生存情况。
Integr Cancer Ther. 2018 Sep;17(3):986-993. doi: 10.1177/1534735417747984. Epub 2017 Dec 19.
4
Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy.低剂量纳曲酮上调正常剂量时未出现的独特基因表达:对其在癌症治疗中的应用意义。
Int J Oncol. 2016 Aug;49(2):793-802. doi: 10.3892/ijo.2016.3567. Epub 2016 Jun 7.
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Duration of opioid receptor blockade determines biotherapeutic response.阿片受体阻断的持续时间决定生物治疗反应。
Biochem Pharmacol. 2015 Oct 1;97(3):236-46. doi: 10.1016/j.bcp.2015.06.016. Epub 2015 Jun 25.
6
The mu opioid receptor: A new target for cancer therapy?μ 阿片受体:癌症治疗的新靶点?
Cancer. 2015 Aug 15;121(16):2681-8. doi: 10.1002/cncr.29460. Epub 2015 Jun 4.
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Long-term remission of adenoid cystic tongue carcinoma with low dose naltrexone and vitamin D3--a case report.低剂量纳曲酮与维生素D3联合治疗腺样囊性舌癌长期缓解——病例报告
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Routine piloting in systematic reviews--a modified approach?系统评价中的常规预试验——一种改进方法?
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