Cutaneous melanoma represents the fifth tumor in terms of incidence in young adults, with a major involvement of males than females. Despite the significant changes in available effective treatments for cutaneous melanoma, there is still a proportion of patients that do not benefit long-term disease control with immune checkpoint inhibitors and/or BRAF/MEK inhibitors, and eventually develop progressive disease. In addition to the emerging biomarkers under investigation to understand resistance to treatments, recent studies resumed the role of sex hormones (estrogens, progesterone and androgens) in melanoma patients. In the last decades, the impact of sex hormones has been considered controversial in melanoma patients, but actual growing preclinical and clinical evidence underline the potential influence on melanoma cells’ growth, tumor microenvironment, the immune system and consequently on the course of disease.This review will provide available insights on the role of sex hormones in melanoma pathogenesis, disease progression and response/resistance to systemic treatments. We will also offer an overview on the recent studies on the theme, describing the hormonal contribution to disease response and the interaction with targeted therapies and immune-checkpoint inhibitors in cutaneous melanoma patients, illustrating an insight into future research in this field.

中文翻译：

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黑色素瘤和性激素：发病机制、进行性疾病和治疗反应

就年轻人的发病率而言，皮肤黑色素瘤是第五大肿瘤，其中男性多于女性。尽管皮肤黑色素瘤的有效治疗方法发生了重大变化，但仍有一部分患者无法从免疫检查点抑制剂和/或 BRAF/MEK 抑制剂的长期疾病控制中获益，并最终发展为进行性疾病。除了正在研究新兴生物标志物以了解治疗耐药性之外，最近的研究还恢复了性激素（雌激素、孕激素和雄激素）在黑色素瘤患者中的作用。在过去的几十年里，性激素对黑色素瘤患者的影响一直被认为是有争议的，但实际越来越多的临床前和临床证据强调了性激素对黑色素瘤细胞生长、肿瘤微环境、免疫系统以及因此对病程的潜在影响。审查将提供关于性激素在黑色素瘤发病机制、疾病进展和对全身治疗的反应/耐药中的作用的可用见解。我们还将概述该主题的最新研究，描述激素对疾病反应的贡献以及皮肤黑色素瘤患者与靶向治疗和免疫检查点抑制剂的相互作用，阐明对该领域未来研究的见解。