Villanova F, Procopio A, Rippo M R
Laboratory of Experimental Pathology, Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy.
Curr Med Chem. 2008;15(7):631-41. doi: 10.2174/092986708783885273.
Malignant Mesothelioma is an aggressive and fatal type of tumor. The incidence of mesothelioma has increased in the past 30 years and is now common as male cancers of the liver, bone and bladder, especially in Europe and Australia. The main risk factor is asbestos exposure even if other co-factor, such as simian virus 40 (SV40) could be implied in its etiology. Unfortunately, its incidence is expected to continue to increase for the next decades, also in rapidly industrializing countries, such as India, where it is not recognised as an occupational disease. Furthermore, some disastrous events, such as the World Trade Center Disaster, may contribute to increase future risk for mesothelioma. The treatment-resistant phenotype of mesothelioma is largely due to its ability to escape from the highly regulated apoptotic machinery. The understanding of the molecular mechanisms responsible of the malignant mesothelioma resistance to apoptosis is now advancing, allowing developing new therapeutic strategies to change the natural history and improve survival of patients. This review gives an overview of the main anti-apoptotic strategies devised by malignant mesothelioma and the therapeutic implication and opportunities for this cancer.
恶性间皮瘤是一种侵袭性且致命的肿瘤类型。在过去30年中,间皮瘤的发病率有所上升,如今已与男性的肝癌、骨癌和膀胱癌发病率相当,在欧洲和澳大利亚尤为常见。主要风险因素是石棉暴露,即便其他协同因素,如猿猴病毒40(SV40)可能也涉及其病因。不幸的是,预计在未来几十年里,其发病率仍将持续上升,在印度等快速工业化国家亦是如此,在这些国家间皮瘤未被认定为职业病。此外,一些灾难性事件,如世贸中心灾难,可能会增加未来患间皮瘤的风险。间皮瘤的治疗抵抗表型很大程度上归因于其逃避高度调控的凋亡机制的能力。目前对恶性间皮瘤抗凋亡的分子机制的理解正在推进,这使得开发新的治疗策略以改变其自然病程并提高患者生存率成为可能。本文综述了恶性间皮瘤所采用的主要抗凋亡策略及其对该癌症的治疗意义和机遇。