Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Department of Sense Organs, Sapienza University of Rome, Rome, Italy.
J Exp Clin Cancer Res. 2021 May 8;40(1):159. doi: 10.1186/s13046-021-01926-6.
Hypoxia, a condition of low oxygen availability, is a hallmark of tumour microenvironment and promotes cancer progression and resistance to therapy. Many studies reported the essential role of hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry and response to therapy in melanoma. Melanoma is an aggressive cancer originating from melanocytes located in the skin (cutaneous melanoma), in the uveal tract of the eye (uveal melanoma) or in mucosal membranes (mucosal melanoma). These three subtypes of melanoma represent distinct neoplasms in terms of biology, epidemiology, aetiology, molecular profile and clinical features.In this review, the latest progress in hypoxia-regulated pathways involved in the development and progression of all melanoma subtypes were discussed. We also summarized current knowledge on preclinical studies with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis or vasculogenic mimicry. Finally, we described available evidence on clinical studies investigating the use of Hypoxia-Inducible Factor-1 inhibitors or antiangiogenic drugs, alone or in combination with other strategies, in metastatic and adjuvant settings of cutaneous, uveal and mucosal melanoma.Hypoxia-Inducible Factor-independent pathways have been also reported to regulate melanoma progression, but this issue is beyond the scope of this review.As evident from the numerous studies discussed in this review, the increasing knowledge of hypoxia-regulated pathways in melanoma progression and the promising results obtained from novel antiangiogenic therapies, could offer new perspectives in clinical practice in order to improve survival outcomes of melanoma patients.
缺氧是一种氧气供应不足的情况，是肿瘤微环境的标志，并促进癌症的进展和对治疗的耐药性。许多研究报告了缺氧在调节黑色素瘤侵袭性、血管生成、血管生成拟态和对治疗的反应中的重要作用。黑色素瘤是一种起源于皮肤（皮肤黑色素瘤）、眼睛葡萄膜（葡萄膜黑色素瘤）或粘膜（粘膜黑色素瘤）中黑素细胞的侵袭性癌症。这三种亚型的黑色素瘤在生物学、流行病学、病因学、分子谱和临床特征方面代表了不同的肿瘤。在这篇综述中，讨论了缺氧调节途径在所有黑色素瘤亚型的发展和进展中的最新进展。我们还总结了目前关于靶向缺氧诱导因子-1、血管生成或血管生成拟态的药物的临床前研究的知识。最后，我们描述了在转移性和辅助性皮肤、葡萄膜和粘膜黑色素瘤中使用缺氧诱导因子-1抑制剂或抗血管生成药物，单独或联合其他策略的临床研究中可用的证据。已经报道了缺氧非依赖性途径也可以调节黑色素瘤的进展，但这个问题超出了本文的范围。从本文讨论的众多研究中可以明显看出，缺氧调节途径在黑色素瘤进展中的认识不断提高，以及新型抗血管生成疗法的有希望的结果，为改善黑色素瘤患者的生存结果提供了新的临床实践视角。
