Skip to main content
Erschienen in: Advances in Therapy 2/2021

18.12.2020 | Review

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

verfasst von: Karina Liubchenko, Kevin Kordbacheh, Nika Khajehdehi, Tanja Visnjevac, Frederick Ma, James S. Khan, Myles Storey, Alaa Abd-Elsayed, Ognjen Visnjevac

Erschienen in: Advances in Therapy | Ausgabe 2/2021

Einloggen, um Zugang zu erhalten

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.
Literatur
5.
Zurück zum Zitat Aylsworth CF, Hodson CA, Meites J. Opiate antagonists can inhibit mammary tumor growth in rats. Proc Soc Exp Biol Med. 1979;161(1):18–20.CrossRef Aylsworth CF, Hodson CA, Meites J. Opiate antagonists can inhibit mammary tumor growth in rats. Proc Soc Exp Biol Med. 1979;161(1):18–20.CrossRef
17.
Zurück zum Zitat Khan A. Long-term remission of adenoid cystic tongue carcinoma with low dose naltrexone and vitamin D3–a case report. Oral Health Dent Manag. 2014;13(3):721–4.PubMed Khan A. Long-term remission of adenoid cystic tongue carcinoma with low dose naltrexone and vitamin D3–a case report. Oral Health Dent Manag. 2014;13(3):721–4.PubMed
18.
Zurück zum Zitat Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: intermediate results of a prospective case series. Anticancer Res. 2014;34(2):973–80.PubMed Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: intermediate results of a prospective case series. Anticancer Res. 2014;34(2):973–80.PubMed
23.
Zurück zum Zitat Lissoni P, Meregalli S, Fossati V, et al. Radioendocrine therapy of brain tumors with the long acting opioid antagonist naltrexone in association with radiotherapy. Tumori. 1993;79(3):198–201.CrossRef Lissoni P, Meregalli S, Fossati V, et al. Radioendocrine therapy of brain tumors with the long acting opioid antagonist naltrexone in association with radiotherapy. Tumori. 1993;79(3):198–201.CrossRef
25.
Zurück zum Zitat Miskoff JA, Chaudhri M. Low dose naltrexone and lung cancer: a case report and discussion. Cureus. 2018;10(7):e2924.PubMedPubMedCentral Miskoff JA, Chaudhri M. Low dose naltrexone and lung cancer: a case report and discussion. Cureus. 2018;10(7):e2924.PubMedPubMedCentral
26.
Zurück zum Zitat Lissoni P, Malugani F, Bordin V, Conti A, Maestroni G, Tancini G. A new neuroimmunotherapeutic strategy of subcutaneous low-dose interleukin-2 plus the long-acting opioid antagonist naltrexone in metastatic cancer patients progressing on interleukin-2 alone. Neuro Endocrinol Lett. 2002;23(3):255–8.PubMed Lissoni P, Malugani F, Bordin V, Conti A, Maestroni G, Tancini G. A new neuroimmunotherapeutic strategy of subcutaneous low-dose interleukin-2 plus the long-acting opioid antagonist naltrexone in metastatic cancer patients progressing on interleukin-2 alone. Neuro Endocrinol Lett. 2002;23(3):255–8.PubMed
27.
Zurück zum Zitat Lissoni P, Malugani F, Malysheva O, et al. Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system. Neuro Endocrinol Lett. 2002;23(4):341–4.PubMed Lissoni P, Malugani F, Malysheva O, et al. Neuroimmunotherapy of untreatable metastatic solid tumors with subcutaneous low-dose interleukin-2, melatonin and naltrexone: modulation of interleukin-2-induced antitumor immunity by blocking the opioid system. Neuro Endocrinol Lett. 2002;23(4):341–4.PubMed
29.
Zurück zum Zitat McLaughlin PJ, Levin RJ, Zagon IS. Opioid growth factor (OGF) inhibits the progression of human squamous cell carcinoma of the head and neck transplanted into nude mice. Cancer Lett. 2003;199(2):209–17.CrossRef McLaughlin PJ, Levin RJ, Zagon IS. Opioid growth factor (OGF) inhibits the progression of human squamous cell carcinoma of the head and neck transplanted into nude mice. Cancer Lett. 2003;199(2):209–17.CrossRef
30.
Zurück zum Zitat Koo KL, Tejwani GA, Abou-Issa H. Relative efficacy of the opioid antagonist, naltrexone, on the initiation and promotion phases of rat mammary carcinogenesis. Anticancer Res. 1996;16(4A):1893–8. http://ar.iiarjournals.org/. Accessed 25 Jan 2018. Koo KL, Tejwani GA, Abou-Issa H. Relative efficacy of the opioid antagonist, naltrexone, on the initiation and promotion phases of rat mammary carcinogenesis. Anticancer Res. 1996;16(4A):1893–8. http://​ar.​iiarjournals.​org/​. Accessed 25 Jan 2018.
33.
Zurück zum Zitat Aboalsoud A, El-Ghaiesh SH, Abd Elmonem FF, Salem ML, Abdel Rahman MN. The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: the role of OGFr, BCL2, and immune response. Int Immunopharmacol. 2020;78:106068.CrossRef Aboalsoud A, El-Ghaiesh SH, Abd Elmonem FF, Salem ML, Abdel Rahman MN. The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: the role of OGFr, BCL2, and immune response. Int Immunopharmacol. 2020;78:106068.CrossRef
39.
Zurück zum Zitat Machado MC, da Costa-Neto JM, Portela RD, et al. The effect of naltrexone as a carboplatin chemotherapy-associated drug on the immune response, quality of life and survival of dogs with mammary carcinoma. PLoS One. 2018;13(10):e0204830.CrossRef Machado MC, da Costa-Neto JM, Portela RD, et al. The effect of naltrexone as a carboplatin chemotherapy-associated drug on the immune response, quality of life and survival of dogs with mammary carcinoma. PLoS One. 2018;13(10):e0204830.CrossRef
40.
43.
Zurück zum Zitat Zagon IS, Hytrek SD, McLaughlin PJ. Opioid growth factor tonically inhibits human colon cancer cell proliferation in tissue culture. Am J Physiol. 1996;271(3 Pt 2):R511–8.PubMed Zagon IS, Hytrek SD, McLaughlin PJ. Opioid growth factor tonically inhibits human colon cancer cell proliferation in tissue culture. Am J Physiol. 1996;271(3 Pt 2):R511–8.PubMed
49.
Zurück zum Zitat Ma M, Wang X, Liu N, Shan F, Feng Y. Low-dose naltrexone inhibits colorectal cancer progression and promotes apoptosis by increasing M1-type macrophages and activating the Bax/Bcl-2/caspase-3/PARP pathway. Int immunopharmacology. 2020;83:106388.CrossRef Ma M, Wang X, Liu N, Shan F, Feng Y. Low-dose naltrexone inhibits colorectal cancer progression and promotes apoptosis by increasing M1-type macrophages and activating the Bax/Bcl-2/caspase-3/PARP pathway. Int immunopharmacology. 2020;83:106388.CrossRef
Metadaten
Titel
Naltrexone’s Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures
verfasst von
Karina Liubchenko
Kevin Kordbacheh
Nika Khajehdehi
Tanja Visnjevac
Frederick Ma
James S. Khan
Myles Storey
Alaa Abd-Elsayed
Ognjen Visnjevac
Publikationsdatum
18.12.2020
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 2/2021
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-020-01591-9

Weitere Artikel der Ausgabe 2/2021

Advances in Therapy 2/2021 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.