类器官在妇科恶性肿瘤药物筛选中的应用

Application of organoids in drug screening of gynecological malignant tumors

妇科恶性肿瘤是威胁女性生命健康的重大疾病之一,其发病率和死亡率在女性各类疾病中均位居前列。妇科恶性肿瘤起源于女性生殖器官,通常依据发病部位进行分类,其中卵巢癌(ovarian cancer,OC)、子宫内膜癌(endometrial cancer,EC)及宫颈癌(cervical cancer,CCA)是较为常见的几种类型。目前妇科恶性肿瘤多采用以手术、化疗及放疗为主的综合治疗,其中药物在治疗过程中发挥着至关重要的作用。然而,实际临床治疗效果常受到多种因素影响,如药物毒性导致的不良反应和部分患者对药物的耐药性、不敏感性,这些因素都限制了患者生存率的提高。最新研究表明,同一类型的肿瘤在不同个体间呈现出显著的生物学特性和药物反应异质性,这是导致临床上对同一种妇科恶性肿瘤采用相同药物治疗方法却产生不同治疗效果的重要原因。因此,为了实现妇科恶性肿瘤的个体化精准治疗,迫切需要建立与人类肿瘤高度相似的体外模型进行临床研究。药物筛选是一种用于识别和评估具有药物活性及潜在治疗作用化合物的技术,其通过对不同药物在特定条件下的作用效果进行评估,可为医师提供科学的用药指导,避免盲目试药,减少患者的治疗痛苦和经济负担。类器官模型作为药物筛选和个性化医疗的一种创新手段,在探究妇科恶性肿瘤治疗方面进行了广泛研究。类器官是一种在体外由干细胞进行三维培养而形成的具有一定空间结构的组织类似物,能高度模拟体内组织结构及功能,并展现出与人体器官极为相似的组织学和基因型特征。它在很大程度上克服了患者源性癌细胞模型、患者源性异种移植瘤模型等传统肿瘤模型的局限性,已成为肿瘤学领域的重要研究工具,为妇科恶性肿瘤药物筛选研究搭建了一个更具生理学相关性的实验平台。因此,本文将对几种临床前癌症模型的优缺点进行比较,回顾类器官技术的发展历程,阐述妇科肿瘤类器官的建立以及其在OC、EC及CCA药物筛选中的应用,同时探讨类器官技术在当前应用中存在的局限性和未来的发展愿景,旨在为未来的医学研究,特别是新药研究和个性化医疗研究带来启示。

Gynecologic malignant tumors are among the leading diseases threatening women’s lives and health,with the highest morbidity and mortality rates among all female diseases.These tumors originate from female reproductive organs and are typically classified based on the affected site.Ovarian cancer(OC),endometrial cancer(EC)and cervical cancer(CCA)are the most common types.Currently,gynecologic malignant tumors are primarily treated with a combination of surgery,chemotherapy and radiotherapy,where drugs play a critical role in the treatment process.However,the actual clinical effectiveness is often influenced by various factors,such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients,which limit improvements in patient survival rates.Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals,which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor.To achieve individualized and precise treatment for gynecologic malignant tumors,there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research.Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects,providing doctors with scientific guidance on drug use,thereby avoiding blind drug testing and reducing patients'therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions.Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies.Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture,capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs.This approach has largely overcome the limitations of traditional tumor models,such as patient-derived cancer cell models and patient-derived tumor xenograft models,becoming an essential research tool in oncology.It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies.This paper compared the advantages and disadvantages of several preclinical cancer models,reviewed the development process of organoids,and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian,endometrial,and cervical cancers.Additionally,we discussed the current limitations of organoid technology in its application and envisioned its future development,aiming to provide insights for future medical research,particularly in new drug discovery and personalized medicine.