Normandie University, UNICAEN, CNRS, ISTCT Unit, Avenue H. Becquerel, 14074, Caen, France.
Department of Pathology, CHU de Caen, Caen, France.
Target Oncol. 2022 Jul;17(4):407-431. doi: 10.1007/s11523-022-00900-2. Epub 2022 Jul 30.
Malignant pleural mesothelioma is a rare and aggressive neoplasm, which has primarily been attributed to the exposure to asbestos fibers (83% of cases); yet, despite a ban of using asbestos in many countries, the incidence of malignant pleural mesothelioma failed to decline worldwide. While little progress has been made in malignant pleural mesothelioma diagnosis, bevacizumab at first, then followed by double immunotherapy (nivolumab plus ipilumumab), were all shown to improve survival in large phase III randomized trials. The morphological analysis of the histological subtyping remains the primary indicator for therapeutic decision making at an advanced disease stage, while a platinum-based chemotherapy regimen combined with pemetrexed, either with or without bevacizumab, is still the main treatment option. Consequently, malignant pleural mesothelioma still represents a significant health concern owing to poor median survival (12-18 months). Given this context, both diagnosis and therapy improvements require better knowledge of the molecular mechanisms underlying malignant pleural mesothelioma's carcinogenesis and progression. Hence, the Hippo pathway in malignant pleural mesothelioma initiation and progression has recently received increasing attention, as the aberrant expression of its core components may be closely related to patient prognosis. The purpose of this review was to provide a critical analysis of our current knowledge on these topics, the main focus being on the available evidence concerning the role of each Hippo pathway's member as a promising biomarker, enabling detection of the disease at earlier stages and thus improving prognosis.
恶性胸膜间皮瘤是一种罕见且侵袭性的肿瘤，主要归因于暴露于石棉纤维（83%的病例）；然而，尽管许多国家已经禁止使用石棉，但恶性胸膜间皮瘤的发病率在全球范围内并未下降。虽然在恶性胸膜间皮瘤的诊断方面几乎没有取得进展，但贝伐单抗最初，然后是双免疫疗法（纳武单抗加伊匹单抗），都在大型 III 期随机试验中显示出改善生存的效果。在晚期疾病阶段，组织学分型的形态分析仍然是治疗决策的主要指标，而顺铂为基础的化疗方案联合培美曲塞，无论是否联合贝伐单抗，仍然是主要的治疗选择。因此，恶性胸膜间皮瘤仍然是一个重大的健康问题，因为中位生存期较短（12-18 个月）。鉴于这种情况，诊断和治疗的改善都需要更好地了解恶性胸膜间皮瘤发生和进展的分子机制。因此，Hippo 通路在恶性胸膜间皮瘤的发生和进展中最近受到了越来越多的关注，因为其核心成分的异常表达可能与患者的预后密切相关。本综述的目的是对我们目前关于这些主题的知识进行批判性分析，主要关注每个 Hippo 通路成员作为有前途的生物标志物的作用的现有证据，从而能够更早地发现疾病，从而改善预后。
