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类器官作为恶性胸膜间皮瘤精准医学的模型:我们目前进展如何?

Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?

作者信息

Gao Yanyun, Kruithof-de Julio Marianna, Peng Ren-Wang, Dorn Patrick

机构信息

Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland.

Department of BioMedical Research (DBMR), Oncology-Thoracic Malignancies (OTM), University of Bern, 3008 Bern, Switzerland.

出版信息

Cancers (Basel). 2022 Aug 2;14(15):3758. doi: 10.3390/cancers14153758.

Abstract

MPM is an aggressive tumor originating from pleural mesothelial cells. A characteristic feature of the disease is the dominant prevalence of therapeutically intractable inactivating alterations in TSGs, making MPM one of the most difficult cancers to treat and the epitome of a cancer characterized by a significant lack of therapy options and an extremely poor prognosis (5-year survival rate of only 5% to 10%). Extensive interpatient heterogeneity poses another major challenge for targeted therapy of MPM, warranting stratified therapy for specific subgroups of MPM patients. Accurate preclinical models are critical for the discovery of new therapies and the development of personalized medicine. Organoids, an in vitro 'organ-like' 3D structure derived from patient tumor tissue that faithfully mimics the biology and complex architecture of cancer and largely overcomes the limitations of other existing models, are the next-generation tumor model. Although organoids have been successfully produced and used in many cancers, the development of MPM organoids is still in its infancy. Here, we provide an overview of recent advances in cancer organoids, focusing on the progress and challenges in MPM organoid development. We also elaborate the potential of MPM organoids for understanding MPM pathobiology, discovering new therapeutic targets, and developing personalized treatments for MPM patients.

摘要

恶性胸膜间皮瘤(MPM)是一种起源于胸膜间皮细胞的侵袭性肿瘤。该疾病的一个特征是肿瘤抑制基因(TSG)中治疗上难以处理的失活改变占主导地位,这使得MPM成为最难治疗的癌症之一,也是一种治疗选择严重缺乏且预后极差(5年生存率仅为5%至10%)的癌症的典型代表。患者间广泛的异质性给MPM的靶向治疗带来了另一个重大挑战,这就需要对MPM患者的特定亚组进行分层治疗。准确的临床前模型对于发现新疗法和开发个性化医疗至关重要。类器官是一种源自患者肿瘤组织的体外“器官样”三维结构,它能忠实地模拟癌症的生物学特性和复杂结构,并在很大程度上克服了其他现有模型的局限性,是下一代肿瘤模型。尽管类器官已在多种癌症中成功构建并应用,但MPM类器官的开发仍处于起步阶段。在此,我们概述了癌症类器官的最新进展,重点关注MPM类器官开发的进展和挑战。我们还阐述了MPM类器官在理解MPM病理生物学、发现新治疗靶点以及为MPM患者开发个性化治疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c06/9367391/073f118aabdc/cancers-14-03758-g001.jpg

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