PDF(Pubmed)
Abstract：
The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.
摘要：
黑色素瘤的发病率,最致命的皮肤癌,由于紫外线照射而增加。晚期黑色素瘤的治疗，特别是转移性病例，结果不佳仍然具有挑战性。涉及BRAF/MEK抑制剂的靶向治疗和基于抗PD1/抗CTLA4抗体的免疫疗法已经实现了晚期黑色素瘤患者约50%的长期生存率。然而,治疗抵抗和治疗反应不足继续阻碍了提高生存率的治疗方法的进一步突破.这篇综述介绍了黑色素瘤的分子水平发病机制，并概述了当前的治疗选择及其局限性。细胞可因意外或调节的细胞死亡(RCD)而死亡。RCD是由多种大分子控制的有序细胞死亡，以维持内环境的稳定。由于肿瘤细胞不受控制的增殖需要逃避RCD程序，诱导黑素瘤细胞的RCD可能是一种治疗策略。本文综述了各种类型的非凋亡RCDs的研究，如自噬依赖性细胞死亡，坏死,铁性凋亡,焦亡,以及最近发现的角化突起,在黑色素瘤的背景下。检查了这些RCDs与黑色素瘤之间的关系，并讨论了这些RCD与黑色素瘤患者的免疫治疗或靶向治疗之间的相互作用。鉴于这些发现表明黑色素瘤细胞在响应与这些RCD相关的不同刺激时死亡，RCD的诱导有望成为黑色素瘤治疗策略的组成部分.
