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A Review on Cancer Progression - Related Pineal Endocrine Deficiency: Possible Mechanisms and Clinical Implications

Lissoni P and Rovelli F

Several experimental studies have demonstrated the existence of a natural immunobiological resistance cancer growth, which is mediated by both immune and neuroendocrine mechanism. Moreover, further researches have shown that the pineal gland plays a fundamental role in the natural antitumor resistance, by representing the most important anti-cancer organ in the human body. The anticancer property of the pineal gland is due to the production of several anticancer molecules, including the indole hormone melatonin (MLT), which represent the most investigated pineal hormone, other indoles, such as the 5-methoxytryptamine, and beta-carbolines. MLT has been proven to play anticancer activity through several mechanisms, consisting of cytotoxic antiproliferative action and stimulation of the anticancer immunity, by promoting IL-2 production by T helper lymphocytes and IL-12 secretion by dendritic cells. Cancer-progression has appeared to be associated with a progressive decline in MLT nocturnal production. Then, the pineal failure would constitute the main cancer-related endocrine deficiency. Preliminary clinical studies have demonstrated that MLT therapy at mild pharmacological doses may prolong the survival time of metastatic cancer patients, for whom no other effective standard therapy was available, and improve their clinical status. Therefore, a neuroendocrine therapy with MLT and other pineal hormones could constitute a new strategy in cancer treatment, either as a substitutive therapy of cancer-related MLT diminished endogenous production, or to employ its antitumor pharmacological properties.