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从切除到免疫:现代黑色素瘤治疗的全谱系

英文原题:From Excision to Immunity: The Full Spectrum of Modern Melanoma Treatments.

查看英文原题

From Excision to Immunity: The Full Spectrum of Modern Melanoma Treatments.

PubMed 2026/06/24(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

皮肤黑色素瘤是一种生物学上异质性强的恶性肿瘤。

中文摘要

皮肤黑色素瘤是一种生物学上异质性很强的恶性肿瘤。尽管近年来的治疗进展改善了生存率,但许多患者仍难以实现持久缓解。以分期适当切缘进行手术切除并选择性进行淋巴结分期,仍是根治性治疗管理的基石。相比之下,传统细胞毒性化疗由于疗效有限且毒性显著,目前仅发挥有限的、主要为姑息性的作用。BRAF/MEK抑制剂靶向治疗改善了BRAF V600突变型黑色素瘤患者的结局,可实现快速肿瘤消退并带来有意义的生存获益。然而,长期疾病控制常因适应性耐药而受损,这种耐药通常由MAPK通路再激活或代偿性PI3K/AKT信号驱动。与此同时,靶向PD-1、CTLA-4及新兴通路的免疫检查点抑制剂重塑了各疾病阶段的治疗格局,使患者能够获得深度且有时持久的缓解。尽管取得了这些进展,原发性和获得性耐药,以及急性和慢性免疫相关毒性,仍构成重大的临床挑战。当前的治疗策略聚焦于靶向治疗、检查点阻断、基于IL-2的方法、溶瘤病毒以及过继性细胞疗法(如TIL(肿瘤浸润淋巴细胞)的合理联合,以增强缓解深度和持久性。然而,这些强化方案带来更高的毒性风险,凸显了改进患者筛选和监测的必要性。总体而言,新出现的证据支持向优化治疗序贯、应答适应性手术策略以及生物标志物指导的个体化治疗转变,以在最大化临床获益的同时尽量减少毒性。

展开英文摘要原文

Cutaneous Melanoma is a biologically heterogeneous malignancy. Although recent therapeutic advances have improved survival, durable remissions remain elusive for many patients. Surgical excision with stage-appropriate margins and selective nodal staging remains the cornerstone of curative-intent management. In contrast, conventional cytotoxic chemotherapy now plays a limited, largely palliative role given its modest efficacy and substantial toxicity. Targeted therapy with BRAF/MEK inhibitors has improved outcomes in patients with BRAF V600-mutant melanoma, resulting in rapid tumor regression and meaningful survival benefits. However, long-term disease control is frequently compromised by adaptive resistance, commonly driven by MAPK pathway reactivation or compensatory PI3K/AKT signaling. In parallel, immune checkpoint inhibitors targeting PD-1, CTLA-4, and emerging pathways have reshaped treatment across disease stages, enabling deep and sometimes durable responses. Despite this progress, primary and acquired resistance, as well as acute and chronic immune-related toxicities, continue to pose significant clinical challenges. Current therapeutic strategies focus on rational combinations of targeted therapy, checkpoint blockade, IL-2-based approaches, oncolytic viruses, and adoptive cell therapies such as tumor-infiltrating lymphocytes to enhance response depth and durability. However, these intensified regimens carry increased toxicity risks, highlighting the need for improved patient selection and monitoring. Overall, emerging evidence supports a paradigm shift toward optimized treatment sequencing, response-adapted surgical strategies, and biomarker-guided personalization to maximize clinical benefit while minimizing toxicity.

论文信息

作者
Murugesan V、Thuraisingam T、Radzioch D
单位
Department of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada.Canada
文献类型
综述
期刊
Cancers2026 Jun 24
原文标识
PubMed 42449588 · DOI 10.3390/cancers18132043