Neuroendocrine Factors in Melanoma Pathogenesis

SIMPLE SUMMARY: Melanoma is a very aggressive and fatal malignant tumor. While curable if diagnosed in its early stages, advanced melanoma, despite the complex therapeutic approaches, is associated with one of the highest mortality rates. Hence, more and more studies have focused on mechanisms that may contribute to melanoma development and progression. Various studies suggest a role played by neuroendocrine factors which can act directly on tumor cells, modulating their proliferation and metastasis capability, or indirectly through immune or inflammatory processes that impact disease progression. However, there are still multiple areas to explore and numerous unknown features to uncover. A detailed exploration of the mechanisms by which neuroendocrine factors can influence the clinical course of the disease could open up new areas of biomedical research and may lead to the development of new therapeutic approaches in melanoma. ABSTRACT: Melanoma is one of the most aggressive skin cancers with a sharp rise in incidence in the last decades, especially in young people. Recognized as a significant public health issue, melanoma is studied with increasing interest as new discoveries in molecular signaling and receptor modulation unlock innovative treatment options. Stress exposure is recognized as an important component in the immune-inflammatory interplay that can alter the progression of melanoma by regulating the release of neuroendocrine factors. Various neurotransmitters, such as catecholamines, glutamate, serotonin, or cannabinoids have also been assessed in experimental studies for their involvement in the biology of melanoma. Alpha-MSH and other neurohormones, as well as neuropeptides including substance P, CGRP, enkephalin, beta-endorphin, and even cellular and molecular agents (mast cells and nitric oxide, respectively), have all been implicated as potential factors in the development, growth, invasion, and dissemination of melanoma in a variety of in vitro and in vivo studies. In this review, we provide an overview of current evidence regarding the intricate effects of neuroendocrine factors in melanoma, including data reported in recent clinical trials, exploring the mechanisms involved, signaling pathways, and the recorded range of effects.