Cancer is one of the leading causes of morbidity and mortality worldwide. It was already before the last covid-19 pandemic, but worsening of patients and delayed diagnoses made the situation worse. According to the International Agency for Research on Cancer, the most common cancers today include colon and rectum, prostate, breast, lung and bladder cancers.

Global projections suggest that the number of cases will continue to rise, let alone fall, over the next two decades. While prevention and early detection programs will greatly increase patients’ life expectancy, we recognize that clinical management needs to be significantly improved if we are to beat 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 therefore has to be differentiated and this makes it very complex. Although great advances have been made in early diagnosis and increasingly selective targeted therapies in recent years, we recognize that there is still a long way to go before effective pharmacological treatments are available.

Basically, melatonin, a natural-origin bioactive molecule known for its regulatory role in the sleep/wake cycle and its antioxidant activity, also stands out with its important anti-cancer properties. Numerous experimental data indicate that it can slow cancer progression at different stages of the tumor cycle, from initial cell transformation to metastasis.

Specifically, melatonin inhibits cell division (antimitogenic) and the formation of new blood vessels (antiangiogenic) that feeds cancer. Depending on the type and dose of the tumor, by itself or in combination with other drugs used in chemotherapy, it has the potential to inhibit the onset of tumors and the therapeutic capacity to slow malignant progression and metastatic spread.

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a smart killer

Another interesting possibility is the inclusion of melatonin in treatments designed according to the parameters of the circadian system (oncochronotherapies), which succeed in increasing the efficacy and tolerability of drugs. Even in cancerous processes unresponsive to melatonin, it has been shown that this molecule can sensitize cancer cells and sensitize formerly chemoresistant tumors to radio/chemotherapy, increasing the efficacy of radio/chemotherapy treatments.

A particularly relevant finding is that melatonin has shown these benefits in both animal and human studies at a wide range of concentrations without significant side effects, earning it the nickname “smart killer” (smart killer).

Given its pharmacological activity and clinical efficacy, melatonin deserves to be recognized as 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 myriad benefits of melatonin supplementation for cancer treatment. patients.

In this sense, the strategy of combining chemotherapeutic agents with melatonin may limit the secondary effects of the former on normal cells and allow active doses of 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 developing high-dose combination formulations with melatonin is that they are beneficial for patients by increasing the prescription of chemotherapy and reducing side effects.

The dose to achieve this goal is not yet clear. 1-2 mg (physiological dose) used to regulate sleep disorders may be exceeded and oral doses of 1 mg/kg body weight may be required.

To clear the doubts, we characterize the pharmacokinetic variants of this molecule to decipher how to apply it to maximize the efficacy of chemotherapeutic agents while simultaneously reducing its cytotoxicity. This will not only increase therapeutic efficacy against cancer, but will also improve patients’ well-being and quality of life.

Melatonin as a protective agent?

The production of melatonin in our body decreases with age, which can contribute to making organs more vulnerable to oxidative damage and the development of pathologies, including cancer. Everything suggests that age-related reduction of melatonin is one of the main factors causing immune aging and the development of neoplasms.

In this context, exogenous administration has been shown to increase melatonin subcellular stores. In conclusion, the inclusion of this molecule in conventional anticancer therapy may be a strategy to reduce the molecular damage produced on healthy cells by radio/chemotherapy and thereby increase the efficacy of antitumor therapies, especially in immunocompromised patients.

However, although there is ample scientific evidence for the biosafety of melatonin even at high concentrations, more research is needed to define optimal dosing protocols for each tumor and patient, as well as newly developed formulations.

In addition, randomized clinical trials are required to transfer the therapeutic potential of melatonin to clinical practice.

For this purpose, it is important that health institutions, public administrations and medical institutions consider the use of melatonin reasonable and decide to explore options for melatonin in both cancer treatment and proactive prevention.

Alejandro Romero Martinez, Professor of Toxicology, University of Madrid Complutense; Emilio Gil Martín, Professor of Biochemistry and Molecular Biology, University of Vigo and Francisco López-Muñoz, 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.