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:Beyond approval: a mechanism-based review of novel anti-tumour agents in cervical cancer and when to use them.
宫颈癌仍是女性癌症死亡的主要原因,尽管采用放化疗和贝伐珠单抗治疗,复发或转移性疾病的结局仍然很差。
宫颈癌仍是女性癌症死亡的主要原因之一,尽管采用放化疗和贝伐珠单抗,复发或转移性疾病的结局仍然很差。定义该疾病的HPV驱动生物学特征——病毒E6/E7癌蛋白、炎症微环境和可利用的表面抗原——使得新型全身治疗迅速扩展,然而现有综述往往按类别对这些药物进行编目,或孤立地报告单个试验,使其比较疗效、安全性和临床定位仍未得到解决。在此,我们按作用机制组织新兴抗肿瘤药物,并将其沿转化成熟度梯度排列,从已批准方案到1/2期候选药物再到临床前资产,同时评估疗效和安全性。我们涵盖免疫检查点抑制剂、双特异性抗体、抗体药物偶联物(ADC)、治疗性HPV疫苗和过继细胞治疗,并将中国开发的药物——包括PD-1/CTLA-4双特异性抗体卡度尼利单抗和Nectin-4偶联物9MW2821——整合到全球格局中。与纯粹描述性叙述不同,我们并排比较类别特异性毒性特征和预测性生物标志物,并且最重要的是,将碎片化证据转化为以铂耐药疾病为锚点的耐药导向治疗框架。我们进一步认为,由于不同卫生系统对新批准药物的可及性差异很大,药物被引入的治疗线——而非仅其批准状态——可能影响生存,这是当前指南未回答的决策相关问题。这种基于机制、面向决策的综合旨在指导不同临床环境中的合理药物选择、排序和联合策略。
Cervical cancer remains a leading cause of cancer death in women, and outcomes in recurrent or metastatic disease remain poor despite chemoradiation and bevacizumab. The HPV-driven biology that defines the disease-viral E6/E7 oncoproteins, an inflamed microenvironment and exploitable surface antigens-has enabled a rapid expansion of novel systemic therapies, yet existing reviews tend to catalogue these agents by class or report individual trials in isolation, leaving their comparative efficacy, safety and clinical positioning unresolved. Here we organise emerging anti-tumour agents by mechanism of action and array them along a translational maturity gradient, from approved regimens through phase 1/2 candidates to preclinical assets, appraising efficacy and safety in parallel. We cover immune checkpoint inhibitors, bispecific antibodies, antibody-drug conjugates (ADCs), therapeutic HPV vaccines and adoptive cell therapy, and integrate China-developed agents-including the PD-1/CTLA-4 bispecific cadonilimab and the Nectin-4 conjugate 9MW2821-into the global landscape. Departing from a purely descriptive account, we compare class-specific toxicity profiles and predictive biomarkers side by side and, most importantly, translate the fragmented evidence into a resistance-directed treatment framework anchored on platinum-resistant disease. We further argue that, because access to newly approved agents varies widely between health systems, the line of therapy at which an agent is introduced-rather than its approval status alone-may influence survival, a decision-relevant question that current guidelines leave unanswered. This mechanism-based, decision-oriented synthesis is intended to guide rational agent selection, sequencing and combination strategy across diverse clinical settings.
MEMBER ACCOUNT
登录成功会直接打开下一页。