下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Clinically relevant histopathological features and biomarkers in endometrial cancer.
将组织病理学特征和生物标志物纳入常规临床实践,可以更准确地评估预后,并更合理地选择辅助治疗。越来越多的非解剖学生物标志物正成为子宫内膜癌管理中决策算法不可或缺的一部分。
提供对子宫内膜癌最重要的组织病理学特征和生物标志物的概述,这些特征和生物标志物对预后、治疗反应预测以及辅助治疗决策具有临床相关性。
子宫内膜癌是发达国家女性生殖道最常见的恶性肿瘤。疾病预后不仅取决于解剖学范围,还取决于多种非解剖学因素。组织学肿瘤类型、淋巴血管间隙浸润的存在以及特定的肌层浸润模式(如 MELF 模式)起主要作用。当前的分子分型将子宫内膜癌分为四组(POLEmut、MMRd、NSMP 和 TP53mut),这些组在预后和治疗反应方面存在差异。其他临床适用的生物标志物包括雌激素和孕激素受体、L1CAM、HER2、CA125 和 HE4。新兴研究聚焦于新型生物标志物,如 TROP2、循环肿瘤 DNA(ctDNA)、环状 RNA(circRNA)、TIL(肿瘤浸润淋巴细胞)(TILs)和叶酸受体 α(FRa)。这些标志物能够实现更精确的风险分层,并识别适合靶向治疗的患者。多种生物标志物与临床病理参数的整合进一步提高了风险评估和治疗反应预测的准确性。
OBJECTIVE: To provide an overview of the most important histopathological characteristics and biomarkers of endometrial carcinoma that have clinical relevance for prognosis, prediction of treatment response, and decision-making regarding adjuvant therapy. METHODS AND RESULTS: Endometrial carcinoma represents the most common malignancy of the female reproductive tract in developed countries. Disease prognosis is determined not only by the anatomical extent, but also by a number of non-anatomical factors. The histological tumour type, presence of lymphovascular space invasion, and specific patterns of myometrial invasion (such as the MELF pattern) play major roles. Current molecular classification divides endometrial carcinomas into four groups (POLEmut, MMRd, NSMP, and TP53mut), which differ in prognosis as well as in therapeutic response. Additional clinically applicable biomarkers include oestrogen and progesterone receptors, L1CAM, HER2, CA125, and HE4. Emerging research focuses on novel biomarkers such as TROP2, circulating tumour DNA (ctDNA), circular RNA (circRNA), tumour- -infiltrating lymphocytes (TILs), and folate receptor alpha (FRa). These markers enable more precise risk stratification and identification of patients suitable for targeted therapies. Integration of multiple biomarkers with clinicopathological parameters further enhances the accuracy of risk assessment and prediction of treatment response. CONCLUSION: Incorporating histopathological features and biomarkers into routine clinical practice allows for a more accurate estimation of prognosis and a more rational selection of adjuvant therapy. An increasing number of non-anatomical biomarkers are becoming an integral part of the decision-making algorithm in endometrial carcinoma management.
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