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Current Drug Research Reviews

Editor-in-Chief

ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

Letter Article

Low Doses Naltrexone: The Potential Benefit Effects for its Use in Patients with Cancer

Author(s): Ricardo David Couto and Bruno Jose Dumêt Fernandes*

Volume 13, Issue 2, 2021

Published on: 26 January, 2021

Page: [86 - 89] Pages: 4

DOI: 10.2174/2589977513666210127094222

Price: $65

Open Access Journals Promotions 2
Abstract

Naltrexone (NTX) is an opioid antagonist that inhibits cell proliferation in vivo when administered in low doses. Naltrexone in low doses can reduce tumor growth by interfering with cell signalling as well as by modifying the immune system. It acts as an Opioid Growth Factor receptor (OGFr) antagonist and the OGF-OGFr axis is an inhibitory biological pathway present in human cancer cells and tissues, being a target for the treatment with naltrexone low-dose (LDN). Clinical trials have proposed a unique mechanism(s) allowing LDN to affect tumors. LDN shows promising results for people with primary cancer of the bladder, breast, liver, lung, lymph nodes, colon and rectum. This short review provides further evidence to support the role of LDN as an anticancer agent.

Keywords: Low dose naltrexone, naltrexone, opioid growth factor receptor, cancer, tumor, and treatment.

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Graphical Abstract
[1]
Donahue RN, McLaughlin PJ, Zagon IS. Low-dose naltrexone targets the opioid growth factor-opioid growth factor receptor pathway to inhibit cell proliferation: mechanistic evidence from a tissue culture model. Exp Biol Med (Maywood) 2011; 236(9): 1036-50.
[http://dx.doi.org/10.1258/ebm.2011.011121] [PMID: 21807817]
[2]
Ludwig MD, Zagon IS, McLaughlin PJ. Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Exp Biol Med (Maywood) 2017; 242(15): 1524-33.
[http://dx.doi.org/10.1177/1535370217724791] [PMID: 28766982]
[3]
Smith JP, Bingaman SI, Mauger DT, Harvey HH, Demers LM, Zagon IS. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer. Open Access J Clin Trials 2010; 2010(2): 37-48.
[PMID: 20890374]
[4]
Zagon IS, Donahue R, McLaughlin PJ. Targeting the opioid growth factor: opioid growth factor receptor axis for treatment of human ovarian cancer. Exp Biol Med (Maywood) 2013; 238(5): 579-87.
[http://dx.doi.org/10.1177/1535370213488483] [PMID: 23856908]
[5]
Rogosnitzky M, Finegold MJ, McLaughlin PJ, Zagon IS. Opioid growth factor (OGF) for hepatoblastoma: a novel non-toxic treatment. Invest New Drugs 2013; 31(4): 1066-70.
[http://dx.doi.org/10.1007/s10637-012-9918-3] [PMID: 23275062]
[6]
McLaughlin PJ, Zagon IS. Duration of opioid receptor blockade determines biotherapeutic response. Biochem Pharmacol 2015; 97(3): 236-46.
[http://dx.doi.org/10.1016/j.bcp.2015.06.016] [PMID: 26119823]
[7]
Zagon IS, McLaughlin PJ. Stereospecific modulation of tumorigenicity by opioid antagonists. Eur J Pharmacol 1985; 113(1): 115-20.
[http://dx.doi.org/10.1016/0014-2999(85)90350-4] [PMID: 2995053]
[8]
Cheng F, Zagon IS, Verderame MF, McLaughlin PJ. The opioid growth factor (OGF)-OGF receptor axis uses the p16 pathway to inhibit head and neck cancer. Cancer Res 2007; 67(21): 10511-8.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1922] [PMID: 17974995]
[9]
Zagon IS, McLaughlin PJ. Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer. Life Sci 1984; 35(4): 409-16.
[http://dx.doi.org/10.1016/0024-3205(84)90651-9] [PMID: 6087062]
[10]
Sikora M, Rakowska A, Olszewska M, Rudnicka L. The use of naltrexone in dermatology. current evidence and future directions. Curr Drug Targets 2019; 20(10): 1058-67.
[http://dx.doi.org/10.2174/1389450120666190318121122] [PMID: 30887922]
[11]
Janković BD, Radulović J. Enkephalins, brain and immunity: modulation of immune responses by methionine-enkephalin injected into the cerebral cavity. Int J Neurosci 1992; 67(1-4): 241-70.
[http://dx.doi.org/10.3109/00207459208994788] [PMID: 1305637]
[12]
Li Z, You Y, Griffin N, Feng J, Shan F. Low-dose naltrexone (LDN): a promising treatment in immune-related diseases and cancer therapy. Int Immunopharmacol 2018; 61: 178-84.
[http://dx.doi.org/10.1016/j.intimp.2018.05.020] [PMID: 29885638]
[13]
Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum 2013; 65(2): 529-38.
[http://dx.doi.org/10.1002/art.37734] [PMID: 23359310]
[14]
Amaram-Davila J, Davis M, Reddy A. Opioids and cancer mortality. Curr Treat Options Oncol 2020; 21(3): 22.
[http://dx.doi.org/10.1007/s11864-020-0713-7] [PMID: 32095929]
[15]
Immonen JA, Zagon IS, McLaughlin PJ. Selective blockade of the OGF-OGFr pathway by naltrexone accelerates fibroblast proliferation and wound healing. Exp Biol Med (Maywood) 2014; 239(10): 1300-9.
[http://dx.doi.org/10.1177/1535370214543061] [PMID: 25030485]
[16]
Hytrek SD, McLaughlin PJ, Lang CM, Zagon IS. Inhibition of human colon cancer by intermittent opioid receptor blockade with naltrexone. Cancer Lett 1996; 101(2): 159-64.
[http://dx.doi.org/10.1016/0304-3835(96)04119-5] [PMID: 8620464]
[17]
Zagon IS, McLaughlin PJ. Naltrexone modulates tumor response in mice with neuroblastoma. Science 1983; 221(4611): 671-3.
[http://dx.doi.org/10.1126/science.6867737] [PMID: 6867737]
[18]
Wang D, Du L, Meng Q, Ge Y, Shan F, Su Q. Experimental study on the therapy of pancreatic cancer by combining methionine encephalin with naltrexone. J Modern Oncol 2018; 26: 22-7.
[19]
Garcia JBS, Cardoso MGM, Dos-Santos MC. Opioids and the immune system: clinical relevance. Rev Bras Anestesiol 2012; 62(5): 709-18.
[http://dx.doi.org/10.1016/S0034-7094(12)70169-1] [PMID: 22999403]
[20]
Berkson BM, Rubin DM, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using only low-dose naltrexone. Integr Cancer Ther 2007; 6(3): 293-6.
[http://dx.doi.org/10.1177/1534735407306358] [PMID: 17761642]
[21]
Zagon IS, Donahue RN, McLaughlin PJ. Opioid growth factor-opioid growth factor receptor axis is a physiological determinant of cell proliferation in diverse human cancers. Am J Physiol Regul Integr Comp Physiol 2009; 297(4): R1154-61.
[http://dx.doi.org/10.1152/ajpregu.00414.2009] [PMID: 19675283]
[22]
Liu WM, Scott KA, Dennis JL, Kaminska E, Levett AJ, Dalgleish AG. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: implications for its use in cancer therapy. Int J Oncol 2016; 49(2): 793-802.
[http://dx.doi.org/10.3892/ijo.2016.3567] [PMID: 27279602]
[23]
Bihari B. LDN and cancer. Low Dose Naltrexone Web site http://www.lowdosenaltrexone.org
[24]
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.
[http://dx.doi.org/10.1177/030089169307900308] [PMID: 8236504]
[25]
Berkson BM, Rubin DM, Berkson AJ. The long-term survival of a patient with pancreatic cancer with metastases to the liver after treatment with the intravenous alpha-lipoic acid/low-dose naltrexone protocol. Integr Cancer Ther 2006; 5(1): 83-9.
[http://dx.doi.org/10.1177/1534735405285901] [PMID: 16484716]
[26]
Berkson BM, Rubin DM, Berkson AJ. Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases. Integr Cancer Ther 2009; 8(4): 416-22.
[http://dx.doi.org/10.1177/1534735409352082] [PMID: 20042414]
[27]
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.
[PMID: 25284545]
[28]
Singleton PA, Lingen MW, Fekete MJ, Garcia JG, Moss J. Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvasc Res 2006; 72(1-2): 3-11.
[http://dx.doi.org/10.1016/j.mvr.2006.04.004] [PMID: 16820176]

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