PDF(Pubmed)
Abstract：
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.
摘要：
睾丸核蛋白癌（NC）是一种高度侵袭性的肿瘤疾病。鉴于目前的治疗方案只能提供6个月的中位生存期，这种类型的肿瘤很可能需要扩展的多模式治疗方法来改善预后.在之前的病例报告中,我们可以证明溶瘤单纯疱疹病毒（T-VEC）在NC患者中具有功能。为了确定T-VEC的进一步组合合作伙伴，我们已经研究了T-VEC和5种不同的小分子抑制剂(SMI)在人NC细胞系中单独和组合的抗肿瘤作用。发现与各自的单一疗法相比,双重组合导致更高的肿瘤细胞减少率,如通过活力测定和实时肿瘤细胞生长监测所证明的。有趣的是,我们发现T-VEC与SMI的组合导致c-Myc表达的更强且更早的减少，NC细胞增殖的主要驱动因素，与T-VEC单一疗法相比。这些结果表明，使用溶瘤病毒和SMI的组合疗法具有控制NC癌症的高度攻击行为的巨大潜力，并且可能会在不久的将来为创新的多模式临床研究铺平道路。
