自噬在皮肤黑色素瘤中的双重效应及耐药中的作用研究进展

doi:10.3969/j.issn.1674-8115.2025.02.013

摘要/Abstract

摘要：

皮肤黑色素瘤（cutaneous melanoma，CM）是一种由黑色素细胞恶性增殖引起的高度恶性肿瘤，易发生远处转移，具有高致死率。尽管靶向治疗和免疫治疗的发展显著提高了晚期CM患者的生存率，但肿瘤耐药性限制了治疗效果的进一步提高。近年来，自噬作为一种关键的调节性细胞死亡方式，在CM的致病机制中的作用研究取得了重要进展。自噬是利用溶酶体降解和再循环各种细胞组分维持细胞内环境稳态的主要机制。大量研究证实，自噬在CM中的作用复杂且具有争议性。在肿瘤发展早期阶段，自噬可能通过清除损伤的细胞组分，抑制肿瘤细胞异常增殖。但随着肿瘤的进展，自噬可能发挥促进肿瘤侵袭和转移的作用。在晚期CM中，自噬的激活有助于肿瘤细胞在压力环境下存活。尤其是在鼠类肉瘤病毒癌基因同源物B1（V-Raf murine sarcoma viral oncogene homolog B1，BRAF）突变的CM中，自噬活动常常增强，削弱BRAF抑制剂靶向治疗的效果。该文深入分析自噬在CM进展中的双重效应，并探讨自噬在CM耐药中的作用，以期为开发靶向治疗CM新策略提供参考。

关键词: 皮肤黑色素瘤, 自噬, 自噬相关蛋白, 靶向治疗

Abstract:

Cutaneous melanoma (CM) is a highly malignant tumor caused by malignant proliferation of melanocytes, characterized by distant metastasis and high mortality. Although targeted therapy and immunotherapy have significantly improved the survival rates of advanced CM patients, tumor resistance remains a key barrier to further improving treatment outcomes. In recent years, significant progress has been made in the study of autophagy as a key regulatory cell death mode in the pathogenesis of CM. Autophagy is the main mechanism that mediates the degradation and recycling of various cellular components through lysosomes to maintain the homeostasis of the intracellular environment. A large number of studies have confirmed that the role of autophagy in CM is complex and controversial. In the early stages of CM development, autophagy may inhibit abnormal proliferation of tumor cells by removing damaged cell components. However, as the tumor progresses, autophagy may transform into a role that promotes tumor invasion and metastasis. In advanced CM, the activation of autophagy helps tumor cells survive in stressful environments. In particular, in CM with BRAF (V-Raf murine sarcoma viral oncogene homolog B1) mutations, autophagy activity is often enhanced, weakening the effectiveness of BRAF inhibitor-targeted therapy. This article provides an in-depth analysis of the dual effects of autophagy on the progression of CM and explores the role of autophagy in CM resistance, in order to provide insights for the development of new targeted therapy strategies for CM.

Key words: cutaneous melanoma, autophagy, autophagy-related protein (ATG), targeted therapy

中图分类号:

R739.5

罗文, 吕明君, 张珍, 张雪, 姚志荣. 自噬在皮肤黑色素瘤中的双重效应及耐药中的作用研究进展[J]. 上海交通大学学报（医学版）, 2025, 45(2): 233-240.

LUO Wen, LÜ Mingjun, ZHANG Zhen, ZHANG Xue, YAO Zhirong. Research progress on the dual effects of autophagy in cutaneous melanoma and its role in drug resistance[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(2): 233-240.

图/表 3

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Agent	Autophagy-related mechanism	Phase	Outcome	Refrence
HCQ+TMZ	Inhibit fusion of autophagosome and lysosome	Ⅰ	14% PR, 27% SD	[51]
HCQ+D+T	Inhibit fusion of autophagosome and lysosome	Ⅰ/Ⅱ	85% OR, 41% CR PFS: 11.2 months, OS: 26.5 months	[52-53]
HCQ+D+T	Inhibit fusion of autophagosome and lysosome	Ⅱ	20% OR	[54]
HCQ+ TEM	mTOR inhibitor	Ⅰ	PFS: 3.5 months	[55]

Agent	Autophagy-related mechanism	Phase	Outcome	Refrence
HCQ+TMZ	Inhibit fusion of autophagosome and lysosome	Ⅰ	14% PR, 27% SD	[51]
HCQ+D+T	Inhibit fusion of autophagosome and lysosome	Ⅰ/Ⅱ	85% OR, 41% CR PFS: 11.2 months, OS: 26.5 months	[52-53]
HCQ+D+T	Inhibit fusion of autophagosome and lysosome	Ⅱ	20% OR	[54]
HCQ+ TEM	mTOR inhibitor	Ⅰ	PFS: 3.5 months	[55]

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