Review Article
Paolo Lissoni, Giusy Messina,
Abstract
It is known that the prognosis of the neoplastic diseases does not depend only on tumor characteristics, including lesion extension, histology and genetic profile, but also on the biological response of patients, which depends on both immune and endocrine variables, since the immune system is physiologically under a psychoneuroendocrine regulation. Therefore, a synthetic clinical evaluation of the endocrine and immune functions either prior to the various anticancer therapies or under treatment is essential for realizing an adequate investigation of the mechanisms involved in the clinical course of the neoplastic disease. In more detail, the prognosis of several tumors, irrespectively of their histology and extension, has appeared to be worse in the presence of alterations of cortisol rhythm, a reduced pineal secretion of melatonin during the night, lymphocytopenia, low T-H1 cell count, high T regulatory lymphocyte number, and abnormally high PRL levels for the only metastatic breast and prostate tumors. The pharmacological correction of the main endocrine, neuroendocrine and immune alterations occurring during the clinical course of the neoplastic disease could improve the prognosis and the efficacy of the various anticancer therapies. Moreover, the immune system in vivo is under a physiological psychoneuroendocrine 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 hyper-activity 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, β-carbolines. Moreover, these neuroendocrine combinations may be successfully associated with antitumor cytokines, such as IL-2 and IL-12 as a psychoneuroendocrinoimmune cancer therapy, as well as with antitumor plants as psychoneuroendocrinophytotherapy of cancer, in an attempt to propose possible anticancer treatments also to patients with disseminated cancer and untreatable according to the standard Oncology. The main novelty is to refer the personalization of cancer cure not only in relation to the biogenetic characteristics of the tumor of the single patients, but also to the biological characteristics of each cancer patient, namely the immune status in terms of antitumor immunity.