Cortes-Dericks Lourdes, Galetta Domenico
Department of Biology, University of Hamburg, 20146 Hamburg, Germany.
Division of Thoracic Surgery, San Giovanni Bosco Hospital, 10154 Turin, Italy.
Cancers (Basel). 2025 Mar 14;17(6):979. doi: 10.3390/cancers17060979.
Malignant pleural mesothelioma (PM) is a highly aggressive disease of the lung pleura associated with poor prognosis. Despite advances in improving the clinical management of this malignancy, there is no effective chemotherapy for refractory or relapsing PM. The acquisition of resistance to standard and targeted therapy in this disease is a foremost concern; therefore, a deeper understanding of the complex factors surrounding the emergence of drug resistance is deemed necessary. In this review, we will present broad insights into various cellular and molecular concepts, accounting for the recalcitrance of PM to chemotherapy, including signaling networks regulating drug tolerance, drug resistance-associated proteins, genes, and miRNAs, as well as the critical role of cancer stem cells. Identification of the biological determinants and their associated mechanisms may provide a framework for the development of appropriate treatment.
恶性胸膜间皮瘤（PM）是一种侵袭性很强的肺胸膜疾病，预后较差。尽管在改善这种恶性肿瘤的临床管理方面取得了进展，但对于难治性或复发性PM尚无有效的化疗方法。该疾病对标准治疗和靶向治疗产生耐药性是一个首要问题；因此，深入了解围绕耐药性出现的复杂因素被认为是必要的。在本综述中，我们将对各种细胞和分子概念进行广泛的探讨，以解释PM对化疗的顽固性，包括调节药物耐受性的信号网络、耐药相关蛋白、基因和微小RNA，以及癌症干细胞的关键作用。确定生物学决定因素及其相关机制可能为开发适当的治疗方法提供一个框架。
