Worldwide, cancer is one of the leading causes of morbidity and mortality. It already was before the recent covid-19 pandemic, but the deterioration of patients and the delay in diagnoses has made the situation worse. Among the most common cancers today, according to the International Agency for Research on Cancerare those of the colon and rectum, prostate, breast, lung and urinary bladder.
Global estimates indicate that, far from going down, the number of cases will continue to rise over the next two decades. Although prevention and early detection programs will greatly increase the life expectancy of patients, we are aware that clinical management will need to improve significantly if we want to defeat the disease.
Melatonin as an anticancer
Although the term cancer seems to refer to a single disease, it actually encompasses more than 100 different pathological entities, with different tissues of origin and modes of development. The therapeutic approach must therefore be differentiated and this makes it very complex. Although in recent years enormous progress has been made in early diagnosis and in increasingly selective targeted treatments, we are aware that there is still a long way to go before effective pharmacological treatments are available.
The melatonin, a bioactive molecule of natural origin known mainly for its regulatory role in the sleep/wake cycle and its antioxidant activity, also stands out for its important anti-cancer properties. Numerous experimental data show that it can slow down the progression of cancer at different stages of the tumor cycle, from initial cell transformation to metastasis.
Specifically, melatonin prevents cell division (antimitogenic) and the formation of new blood vessels that nourish the cancer (antiangiogenic). To which is added that, depending on the type of tumor and the dose, either per se o along with other drugs used in chemotherapyhas the potential to prevent tumor initiation, and the therapeutic ability to slow malignant progression and metastatic spread.
a smart killer
Another interesting possibility is to include melatonin in treatments designed according to the parameters of the circadian system (oncochronotherapies), which manage to increase the efficacy and tolerability of drugs. Even in cancerous processes that do not respond to melatonin, it has been shown that this molecule can sensitize cancer cells and enhance the effectiveness of radio/chemotherapy treatments, making previously chemoresistant tumors sensitive to radio/chemotherapy.
A particularly relevant finding is that melatonin has shown these benefits, both in animal and human studies, without significant adverse effects and in a wide range of concentrations, which has earned it the nickname “clever killer”smart killer).
Considering its pharmacological activity and clinical efficacy, melatonin deserves to be considered an important public health resource, as evidenced by the fact that the United States Department of Health has led an in-depth study of the numerous benefits of melatonin supplementation for the treatment of cancer patients.
In this sense, the strategy of combining chemotherapy with melatonin could limit the secondary effects of the former on normal cells, allowing the active doses of the drugs to be increased without exacerbating their toxicity. This safety is crucial for the clinical management of cancer patients. In fact, one of the current challenges in the development of formulations combined with melatonin at high doses is that they are beneficial for patients, mitigating side effects by increasing the prescription of chemotherapy.
The dose to achieve this goal is not yet clear. The 1-2 mg used to regulate sleep disorders (physiological dose) may be exceeded and oral doses of 1 mg/kg body weight may be required.
To dispel doubts, we are characterizing the pharmacokinetic variables of this molecule in order to decipher how to administer it so that the efficacy of chemotherapeutic agents is maximized and its cytotoxicity is reduced at the same time. This will not only improve the therapeutic efficacy against cancer, but also the well-being and quality of life of patients.
Melatonin as a preventive agent?
The production of melatonin in our body decreases with age, which can contribute to organs being more vulnerable to oxidative damage and the development of pathologies, including cancer. Everything indicates that the reduction of melatonin associated with age is one of the main factors causing immunosenescence and development of neoplasms.
In this regard, exogenous administration has been shown to increase subcellular stores of melatonin. Consequently, the inclusion of this molecule in conventional anticancer therapy could be a strategy to reduce the molecular damage produced by radio/chemotherapy on healthy cells and thus enhance the efficacy of antitumor treatments, especially in patients with compromised immunocompetence.
However, despite having a large number of scientific evidence of the biosafety of melatonineven at high concentrations, it is necessary to continue researching to define the optimal dosing protocols for each tumor and patient, as well as new improved formulations.
Additionally, randomized clinical trials are essential to transfer the therapeutic potential of melatonin to clinical practice.
To this end, it is essential that health agencies, public administrations and the medical establishment consider the use of melatonin plausible and decide to explore its options, both in the treatment and in the proactive prevention of cancer.
Alejandro Romero MartinezTitular Professor of Toxicology, Complutense University of Madrid; Emilio Gil MartinProfessor of Biochemistry and Molecular Biology, University of Vigo y Francisco López-MuñozFull Professor of Pharmacology and Vice Chancellor for Research and Science, Camilo Jose Cela University
This article was originally published on The Conversation. read the original.