RESUMO
PURPOSE: To describe the natural growth of vestibular schwannoma in patients with neurofibromatosis type 2 and to predict tumor volume evolution in patients treated with bevacizumab and everolimus. METHODS: Clinical data, including longitudinal tumor volumes in patients treated by bevacizumab (n = 13), everolimus (n = 7) or both (n = 2), were analyzed by means of mathematical modeling techniques. Together with clinical data, data from the literature were also integrated to account for drugs mechanisms of action. RESULTS: We developed a model of vestibular schwannoma growth that takes into account the effect of vascular endothelial growth factors and mammalian target of rapamycin complex 1 on tumor growth. Behaviors, such as tumor growth rebound following everolimus treatment stops, was correctly described with the model. Preliminary results indicate that the model can be used to predict, based on early tumor volume dynamic, tumor response to variation in treatment dose and regimen. CONCLUSION: The developed model successfully describes tumor volume growth before and during bevacizumab and/or everolimus treatment. It might constitute a rational tool to predict patients' response to these drugs, thus potentially improving management of this disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Everolimo/uso terapêutico , Modelos Biológicos , Neurofibromatose 2/tratamento farmacológico , Neuroma Acústico/tratamento farmacológico , Carga Tumoral/efeitos dos fármacos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bevacizumab/administração & dosagem , Bevacizumab/farmacocinética , Criança , Pré-Escolar , Everolimo/administração & dosagem , Everolimo/farmacocinética , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Neurofibromatose 2/complicações , Neurofibromatose 2/metabolismo , Neuroma Acústico/complicações , Neuroma Acústico/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
Malignant pleural mesothelioma (MPM) is a highly lethal cancer with limited therapeutic options. Recent work has focused on the frequent somatic inactivation of two tumor suppressor genes in MPM-NF2 (Neurofibromatosis type 2) and the recently identified BAP1 (BRCA associated protein 1). In addition, germline mutations in BAP1 have been identified that define a new familial cancer syndrome, which includes MPM, ocular melanoma, and other cancers. These recent advances may allow screening of high-risk individuals and the development of new therapies that target key pathways in MPM.