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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Therapeutic strategies of melatonin in cancer patients: a systematic review and meta-analysis

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          Abstract

          Background

          Melatonin (MLT), a kind of neuroendocrine active substance, has been reported to function in the treatment of tumors. However, there remain controversies about the curative effect of MLT in tumors in clinical studies. This study investigates the efficacy of MLT on tumor therapeutic strategies by meta-analysis.

          Methods

          After searching several main literature databases, a total of 5,057 articles were obtained and screened by inclusion and exclusion criteria. The tumor remission rate, overall survival rate, and incidence of side effects were recorded and analyzed in the included study patients. Group analysis and sensitivity analysis were performed to examine the sources of heterogeneity in the pooled studies.

          Results

          The tumor remission rate in the MLT group was significantly higher than that in the control group (relative risk [RR] =2.25; 95% CI, 1.86–2.71; P<0.00001; I 2=9%). Likewise, the MLT group had an overall survival rate of 28.24% (n=294/1,041), which was greatly increased compared with the control group (RR =2.07; 95% CI, 1.55–2.76; P<0.00001; I 2=55%). And, MLT could significantly enhance the overall survival rate in non-small-cell lung cancer patients (RR =2.13; 95% CI, 1.41–3.24; P=0.0004; I 2=0%) and various solid tumor patients (RR =2.31; 95% CI, 1.78–2.99; P<0.00001; I 2=0%). It was further proved that MLT could effectively reduce the incidence of neurotoxicity (RR =0.30, 95% CI, 0.19–0.45; P<0.00001), thrombocytopenia (RR =0.23; 95% CI, 0.16–0.33; P<0.00001), and asthenia (RR =0.43, 95% CI, 0.38–0.49; P<0.00001) during chemotherapy.

          Conclusion

          MLT exerts positive influence in tumor therapeutic strategies, including improving tumor remission rate and overall survival rate, while reducing the incidence of chemotherapy side effects. Further large-scale randomized clinical trials (RCTs) are urgently required to verify therapeutic effects of MLT in tumors by various clinical research centers.

          Most cited references44

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          Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

          Russel Reiter, Sergio Rosales-Corral, Dun-Xian Tan … (2017)
          There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.
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            Cancer metastasis: Mechanisms of inhibition by melatonin.

            Shih-Chi Su, Ming-Ju Hsieh, Wei-En Yang … (2017)
            Melatonin is a naturally occurring molecule secreted by the pineal gland and known as a gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple and interrelated mechanisms, exhibits a variety of oncostatic properties in a myriad of tumors during different stages of their progression. Tumor metastasis, which commonly occurs at the late stage, is responsible for the majority of cancer deaths; metastases lead to the development of secondary tumors distant from a primary site. In reference to melatonin, the vast majority of investigations have focused on tumor development and progression at the primary site. Recently, however, interest has shifted toward the role of melatonin on tumor metastases. In this review, we highlight current advances in understanding the molecular mechanisms by which melatonin counteracts tumor metastases, including experimental and clinical observations; emphasis is placed on the impact of both cancer and non-neoplastic cells within the tumor microenvironment. Due to the broad range of melatonin's actions, the mechanisms underlying its ability to interfere with metastases are numerous. These include modulation of cell-cell and cell-matrix interaction, extracellular matrix remodeling by matrix metalloproteinases, cytoskeleton reorganization, epithelial-mesenchymal transition, and angiogenesis. The evidence discussed herein will serve as a solid foundation for urging basic and clinical studies on the use of melatonin to understand and control metastatic diseases.
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              Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials.

              Heidi Fritz, Adam D. Kennedy, Ai-Ping Wu … (2012)
              Melatonin (MLT) is known to possess potent antioxidant, antiproliferative, immune-modulating, and hormone-modulating properties. Clinical evidence suggests that MLT may have a possible role in the treatment of cancer. The authors systematically reviewed the effects of MLT in conjunction with chemotherapy, radiotherapy, supportive care, and palliative care on 1-year survival, complete response, partial response, stable disease, and chemotherapy-associated toxicities. The authors searched 7 databases: MEDLINE (1966-February 2010), AMED (1985-February 2010), Alt HealthWatch (1995-February 2010), CINAHL (1982-February 2010), Nursing and Allied Health Collection: Basic (1985-February 2010), the Cochrane Database (2009), and the Chinese database CNKI (1979-February 2010). They included all trials that randomized patients to treatment, including MLT or a similar control group without MLT. The authors included data from 21 clinical trials, all of which dealt with solid tumors. The pooled relative risk (RR) for 1-year mortality was 0.63 (95% confidence interval [CI] = 0.53-0.74; P < .001). Improved effect was found for complete response, partial response, and stable disease with RRs of 2.33 (95% CI = 1.29-4.20), 1.90 (1.43-2.51), and 1.51 (1.08-2.12), respectively. In trials combining MLT with chemotherapy, adjuvant MLT decreased 1-year mortality (RR = 0.60; 95% CI = 0.54-0.67) and improved outcomes of complete response, partial response, and stable disease; pooled RRs were 2.53 (1.36-4.71), 1.70 (1.37-2.12), and 1.15 (1.00-1.33), respectively. In these studies, MLT also significantly reduced asthenia, leucopenia, nausea and vomiting, hypotension, and thrombocytopenia. MLT may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): OncoTargets and Therapy
                Title: OncoTargets and therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1178-6930
                Publication date Collection: 2018
                Publication date (Electronic): 08 November 2018
                Volume: 11
                Pages: 7895-7908
                Affiliations
                Department of Pharmacy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China, dxsj22@ 123456outlook.com
                Author notes
                Correspondence: Xing Du, Department of Pharmacy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yudong Road, Yantai, Shandong 264000, China, Tel +86 189 0535 1022, Email dxsj22@ 123456outlook.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: ott-11-7895
                DOI: 10.2147/OTT.S174100
                PMC ID: 6231436
                PubMed ID: 30510430
                SO-VID: f544aa1e-0bda-4b7b-808b-d3367a99f003
                Copyright © © 2018 Wang et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mlt,tumor remission rate,overall survival rate,side effects of chemotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: mlt, tumor remission rate, overall survival rate, side effects of chemotherapy

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