The psychoneuroendocrine-immunotherapy of cancer: Historical evolution and clinical results

Abstract

The prognosis of the neoplastic diseases depends not only on the biogenetic characteristics of cancer cells but also on the immunological response of patients, which may influence the biological features of cancer cells themselves as well as the angiogenic processes. Moreover, the immune system in vivo is under a physiological psychoneuroendocrine (PNE) regulation, mainly mediated by the brain opioid system and the pineal gland. In more detail, the anticancer immunity is stimulated by the pineal hormone melatonin (MLT) and inhibited by the opioid system, namely, through a mu-opioid receptor. Several alterations involving the pineal endocrine function and the opioid system have been described in cancer patients, which could play a role in tumor progression itself. Therefore, the pharmacological correction of cancer progression-related anomalies could contribute to control cancer diffusion, namely, the pineal endocrine deficiency and the hyperactivity of brain opioid system. In fact, the administration of pharmacological doses of the only MLT has already been proven to prolong the 1-year survival in untreatable metastatic cancer patients. Better results may be achieved by associating other pineal indoles to MLT, mu-opioid antagonists, cannabinoids, beta-carbolines. Moreover, these neuroendocrine combinations may be successfully associated with antitumor cytokines, such as interleukin (IL)-2 and IL-12, as a PNE-immune cancer therapy as well as with antitumor plants as PNE-phytotherapy of cancer in an attempt to propose possible anticancer treatments also to patients with disseminated cancer and untreatable according to the standard oncology.

The Potential of Integrative Cancer Treatment Using Melatonin and the Challenge of Heterogeneity in Population-Based Studies: A Case Report of Colon Cancer and a Literature Review

“…The anticancer potential of Mel has been shown in many experimental works [16,17,115,116]. The mechanisms of antitumor activity of Mel are associated with pleiotropic effects on cancer cells and the tumor microenvironment, including the induction of apoptosis; anti-inflammatory, anti-angiogenic, antiproliferative, and antimetastatic action; and the regulation of the immune and psychoneuroendocrine systems [33,71,104,115,[117][118][119][120][121][122][123][124][125][126][127][128].…”

“…In a study of 30 patients with metastatic CRC, the authors observed a higher percentage of disease control in the group of patients receiving irinotecan in combination with Mel [121]. The combined use of Mel with CT may increase the survival of patients with advanced non-small cell lung cancer (NSCLC) and gastrointestinal cancer [118,120,127,140]. Adjuvant Mel treatment has no effect on disease-free survival in patients with resected early-stage NSCLC but may confer prolonged survival in those with late-stage disease [141].…”

Relevance of Further Clinical Trials of the Use of Melatonin in Adjuvant Cancer Therapy

“…Двух-и 5-летняя выживаемость пациентов достоверно увеличивалась по сравнению с ХТ без М [15,16]. В опубликованных работах пациенты принимали М перорально в суточных дозах 10-40 мг, а в последних исследованиях -в дозе 100 мг, которая, по мнению авторов, является более эффективной [17]. Таким образом, вопрос об оптимальных дозах М остается открытым.…”

Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged

“…An impressive list of complementary medicines and diets is available and freely accessible to patients. Some of these complementary medicines surely influence the course of the disease or the reactivity of the host [ 169 , 170 , 171 , 172 , 173 ]. It seems impossible to control for this when setting up and running RCTs at present.…”