Psychoneuroendocrinoimmunotherapy of Cancer

Abstract

The overall medical oncological strategies available up to now in the treatment of human neoplasms are performed to counteract cancer dissemination through blocking the proliferation of single cancer cells by several mechanisms. These mechanisms include suppression of angiogenesis, which is essential for cancer growth, inhibition of tumor growth factor receptor expression and protein kinase activation, DNA damage, and induction of apoptosis. However, it has to be noted that tumor growth does not depend only on the genetic characteristics of cancer cells but also on host immune status. Therefore, an evident limitation of anticancer medical therapies such as recent target therapies is neglecting patients’ immune status. Moreover, due to the exclusion of some other fundamental mechanisms, other limitations within the same dynamics of cancer cell proliferation exist such as alterations of the intercellular junctions and the following modifications of the intercellular matrix, which are essential for neoangiogenetic process induction. Several recent clinical studies have demonstrated that at the beginning of the neoplastic disease, there is an immunosuppressive status depending on an altered psychoneuroendocrine regulation of the antitumor immunity, which would be responsible for the evolution of the single transformed cell into a clinically evident tumor mass and substantially consisting of hyperactivation of the brain opioid system associated with a progressive decline in brain cannabinoid system and pineal gland functions. Finally, it has been demonstrated that the great number of cancer-related endocrine, neuroendocrine, and immune alterations involving both cytokine secretion and immune cell differentiation may play a role in promoting cancer dissemination. In more detail, IL-2 and IL-12 deficiencies in association with a progressive decline in pineal endocrine function would represent the main immune and endocrine anomalies, respectively. On this basis, cancer PNEI therapy simply consists of the correction of the main cancer-related immune and neuroendocrine alterations through substitute replacement therapy. At present, promising results in terms of enhanced survival time and improved quality of life have been described by a psychoneuroimmune regimen consisting of subcutaneous low-dose IL-2 and IL-12 in association with antitumor pineal hormones.