靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:Promising New Platforms and Targets in the Management of Gastroesophageal Cancers.
Promising New Platforms and Targets in the Management of Gastroesophageal Cancers.
胃部和胃食管交界处癌症仍然是全球癌症相关死亡的主要原因。
胃和胃食管交界处癌症仍然是全球癌症相关死亡的主要原因。尽管手术和全身治疗取得了逐步进展,但持久生存获益仍然有限,凸显了持续未满足的医疗需求。然而,治疗范式已发生快速转变,这得益于免疫治疗在根治性全身治疗中的整合以及生物标志物引导的全身治疗的扩展。在围手术期,免疫检查点抑制剂联合优化的细胞毒性化疗已显示出令人鼓舞的疗效,近期III期试验有助于确立免疫治疗与化疗联合作为一种新兴治疗平台。在晚期疾病中,精准肿瘤学框架继续扩展到传统生物标志物之外。已确立的靶点如人表皮生长因子受体2现在得到了新验证标志物的补充,包括claudin18.2,而其他可操作改变——如MET和TROP2——正在积极进行临床研究。这些发展正在重新定义治疗算法并引入新的序贯考虑,特别是在肿瘤异质性和生物标志物共表达的背景下。分子诊断和下一代测序的同步进展也促进了治疗相关改变的综合识别。本综述概述了胃和胃食管交界处癌症不断演变治疗格局,涵盖围手术期免疫治疗、新验证的分子靶点以及下一代药物开发平台。通过将生物标志物驱动的策略与创新治疗模式(如抗体-药物偶联物、双特异性抗体、CAR-T 细胞疗法和疫苗)相结合,我们强调了精准治疗如何重塑可切除和晚期疾病的治疗范式。
Gastric and gastroesophageal junction cancers remain a major global cause of cancer-related mortality. Despite incremental advances in surgery and systemic therapy, durable survival gains have been limited, underscoring persistent unmet medical needs. However, the treatment paradigm has undergone a rapid transformation, driven by the integration of immunotherapy in curative-intent systemic treatment and the expansion of biomarker-guided systemic therapies. In the perioperative setting, immune checkpoint inhibitors combined with optimized cytotoxic chemotherapy have demonstrated encouraging efficacy, with recent phase III trials contributing to the establishment of combination of immunotherapy and chemotherapy as an emerging therapeutic platform. In advanced disease, precision oncology frameworks continue to expand beyond traditional biomarkers. Established targets such as human epidermal growth factor receptor 2 are now complemented by newly validated markers including claudin18.2, whereas additional actionable alterations-such as MET and TROP2-are actively under clinical investigation. These developments are redefining treatment algorithms and introducing new sequencing considerations, particularly in the context of tumor heterogeneity and biomarker coexpression. Concurrent advances in molecular diagnostics and next-generation sequencing are also facilitating the comprehensive identification of therapeutically relevant alterations. This review outlines the evolving therapeutic landscape of gastric and gastroesophageal junction cancers, spanning perioperative immunotherapy, newly validated molecular targets, and next-generation drug development platforms. By integrating biomarker-driven strategies with innovative modalities, such as antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor-T-cell therapy, and vaccines, we highlight how precision therapeutics are reshaping treatment paradigms across resectable and advanced disease.
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