Department of Translational Oncology Research, Gene Transfer Laboratory, National Cancer Institute, Largo Rosanna Benzi, 10 16132 Genoa, Italy.
Trends Pharmacol Sci. 2011 Aug;32(8):463-79. doi: 10.1016/j.tips.2011.03.011. Epub 2011 May 26.
Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors.
人恶性胸膜间皮瘤（hMPM）是一种侵袭性的石棉相关癌症，其发病率正在增加，尽管在诊断和治疗方面取得了进展，但预后仍然很差。石棉纤维诱导异常细胞信号转导，导致原癌基因激活和化疗耐药。在这篇综述中，我们讨论了 hMPM 药物治疗的演变，直至最近的进展。单一细胞毒性药物的单药治疗可达到适度的客观缓解率，很少达到 30%。然而，使用新型药物和标准分子的联合方案正在显示出逐渐改善的反应和临床获益。II/III 期研究已经确定培美曲塞作为多靶点叶酸途径抑制剂与铂衍生物联合应用，以及顺铂/吉西他滨联合作为 hMPM 的一线化疗药物。对 hMPM 中信号转导和新生血管形成的分子机制的详细了解，应有助于设计和筛选其他有前途的化合物，如更有效的受体酪氨酸激酶抑制剂。
