Valenza Carmine, Guidi Lorenzo, Battaiotto Elena, Trapani Dario, Sartore Bianchi Andrea, Siena Salvatore, Curigliano Giuseppe
Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Trends Cancer. 2024 Feb;10(2):113-123. doi: 10.1016/j.trecan.2023.11.001. Epub 2023 Nov 25.
About 20% of breast and gastric cancers and 3% of colorectal carcinomas overexpress the human epidermal growth factor receptor 2 (HER2) and are sensitive to HER2-directed agents. The expression of HER2 may differ within the same tumoral lesion (spatial intralesional heterogeneity), from different tumor locations (spatial interlesional heterogeneity), and throughout treatments (temporal heterogeneity). Spatial and temporal heterogeneity may impact on response and resistance to HER2-targeting agents and its prevalence and predictive role changes across HER2-overexpressing solid tumors. Therefore, the definition and the characterization of HER2 heterogeneity pose many challenges and its implementation as a reproducible predictive biomarker would help in guiding treatment modulation.
约20%的乳腺癌和胃癌以及3%的结直肠癌过度表达人表皮生长因子受体2（HER2），并对HER2靶向药物敏感。HER2的表达在同一肿瘤病灶内可能不同（肿瘤内空间异质性），在不同肿瘤部位也可能不同（肿瘤间空间异质性），并且在整个治疗过程中也会变化（时间异质性）。空间和时间异质性可能会影响对HER2靶向药物的反应和耐药性，其发生率以及预测作用在HER2过表达实体瘤中也会发生变化。因此，HER2异质性的定义和特征描述面临诸多挑战，将其作为一种可重复的预测生物标志物加以应用将有助于指导治疗调整。
