RESUMO
Purpose: Finding new treatment options for patients with malignant pleural mesothelioma is challenging due to the rarity and heterogeneity of this cancer type. The absence of druggable targets further complicates the development of new therapies. Current treatment options are therefore limited, and prognosis remains poor.Experimental Design: We performed drug screening on primary mesothelioma cultures to guide treatment decisions of corresponding patients that were progressive after first- or second-line treatment.Results: We observed a high concordance between in vitro results and clinical outcomes. We defined three subgroups responding differently to the anticancer drugs tested. In addition, gene expression profiling yielded distinct signatures that segregated the differently responding subgroups. These genes signatures involved various pathways, most prominently the fibroblast growth factor pathway.Conclusions: Our primary mesothelioma culture system has proved to be suitable to test novel drugs. Chemical profiling of primary mesothelioma cultures allows personalizing treatment for a group of patients with a rare tumor type where clinical trials are notoriously difficult. This personalized treatment strategy is expected to improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7); 1761-70. ©2017 AACRSee related commentary by John and Chia, p. 1513.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , Neoplasias Pleurais/genética , Idoso , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Mesotelioma Maligno , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , PrognósticoRESUMO
Malignant pleural mesothelioma is an aggressive fatal malignancy with a prognosis that has not significantly improved in the last decades. This review summarizes the current state of treatment and the various attempts that are made to improve overall survival for patients with malignant pleural mesothelioma. It also discusses technologies and protocols to test new and hopefully more effective compounds in a more individualized manner. These developments are expected to improve the prognosis for this group of patients.
