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Viruses ; 16(5)2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38793657

RESUMO

NUT (nuclear-protein-in-testis) carcinoma (NC) is a highly aggressive tumor disease. Given that current treatment regimens offer a median survival of six months only, it is likely that this type of tumor requires an extended multimodal treatment approach to improve prognosis. In an earlier case report, we could show that an oncolytic herpes simplex virus (T-VEC) is functional in NC patients. To identify further combination partners for T-VEC, we have investigated the anti-tumoral effects of T-VEC and five different small molecule inhibitors (SMIs) alone and in combination in human NC cell lines. Dual combinations were found to result in higher rates of tumor cell reductions when compared to the respective monotherapy as demonstrated by viability assays and real-time tumor cell growth monitoring. Interestingly, we found that the combination of T-VEC with SMIs resulted in both stronger and earlier reductions in the expression of c-Myc, a main driver of NC cell proliferation, when compared to T-VEC monotherapy. These results indicate the great potential of combinatorial therapies using oncolytic viruses and SMIs to control the highly aggressive behavior of NC cancers and probably will pave the way for innovative multimodal clinical studies in the near future.


Assuntos
Produtos Biológicos , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Vírus Oncolíticos/fisiologia , Vírus Oncolíticos/genética , Terapia Viral Oncolítica/métodos , Linhagem Celular Tumoral , Terapia Combinada , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Carcinoma/terapia , Sobrevivência Celular/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Neoplasias , Herpesvirus Humano 1
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