重新定义化疗和靶向细胞毒性递送在肺神经内分泌肿瘤中的作用
Redefining the Role of Chemotherapy and Targeted Cytotoxic Delivery in Lung Neuroendocrine Tumors.
作者
作者单位
- Humanitas Gavazzeni, Medical Oncology, Bergamo, Italy.
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy.
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy.
摘要
中文
肺神经内分泌肿瘤（NETs）的临床病理学和治疗格局不断演变。尽管系统性化疗历来是治疗基石，但现有数据多为回顾性且过时。对当前文献和公共临床试验注册库进行了批判性综述，以评估化疗和靶向细胞毒性递送系统在肺NETs中的作用。鉴于综述的性质，证据采用描述性综合。在早期疾病中，围手术期（新辅助和辅助）化疗的临床效用仍不确定且缺乏统一标准化。在晚期或转移性情况下，传统的铂类/依托泊苷方案在控制高分化类癌方面疗效欠佳。相反，口服烷化剂（替莫唑胺）和联合方案如CAPTEM（卡培他滨/替莫唑胺）或替莫唑胺联合卡博替尼显示出令人鼓舞的缓解率和疾病控制率。未来策略正从非选择性全身细胞毒性转向靶向递送和化学免疫治疗平台，利用肽-药物偶联物（如PEN-221）、抗体药物偶联物（ADCs）和双特异性T细胞衔接器（BiTEs）靶向新兴表面靶点如DLL3（如tarlatamab）和TROP2。目前迫切需要对前瞻性、多中心临床试验和国际注册库的未满足临床需求。解析肺NETs复杂的分子景观对于识别预测性生物标志物和可操作的治療靶点至关重要，最终将临床管理从经验性、外推的选择转变为基于证据的、分期特定的标准治疗。
English
The clinicopathological and therapeutic landscape of lung neuroendocrine tumors (NETs) is continuously evolving. Although systemic chemotherapy has historically represented a management cornerstone, the available data are predominantly retrospective and outdated. A critical review of the current literature and public clinical trial registries was performed to evaluate the role of chemotherapy and targeted cytotoxic delivery systems in lung NETs. Given the nature of the review, the evidence was synthesized descriptively. In early-stage disease, the clinical utility of perioperative (neoadjuvant and adjuvant) chemotherapy remains uncertain and lacks universal standardization. In the advanced or metastatic setting, traditional platinum/etoposide regimens demonstrate suboptimal efficacy in controlling well-differentiated carcinoids. Conversely, oral alkylating agents (temozolomide) and combination schedules such as CAPTEM (capecitabine/temozolomide) or temozolomide paired with cabozantinib offer promising response and disease control rates. Future strategies are moving away from unselected systemic cytotoxicity toward targeted delivery and chemo-immunotherapy platforms, leveraging peptide-drug conjugates (PDCs like PEN-221), antibody-drug conjugates (ADCs), and bispecific T-cell engagers (BiTEs) directed against emerging surface targets such as DLL3 (e.g., tarlatamab) and TROP2. There is an urgent, unmet clinical need for prospective, multicenter clinical trials and international registries. Dissecting the complex molecular landscape of lung NETs will be essential to identify predictive biomarkers and actionable therapeutic targets, ultimately transitioning clinical management from empirical, extrapolated choices to robust, evidence-based, stage-specific standards of care.
分类与指标
- 研究类型
- 综述Meta
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 2.6
- 新锐分区
- 4区