溶瘤病毒
视网膜母细胞瘤
癌症研究
视网膜母细胞瘤蛋白
帕博西利布
溶瘤腺病毒
E2F型
癌症
生物
细胞周期
病毒复制
病毒学
病毒
乳腺癌
肿瘤细胞
基因
遗传学
转移性乳腺癌
作者
J. Koch,Sebastian Johannes Schober,Sruthi V Hindupur,Caroline Schöning,Florian G Klein,Klaus Mantwill,Maximilian Ehrenfeld,Ulrike Schillinger,Timmy Hohnecker,Qi Pan,Katja Steiger,Michaela Aichler,Jürgen E. Gschwend,Roman Nawroth,Per Sonne Holm
标识
DOI:10.1038/s41467-022-32087-5
摘要
Abstract CDK4/6 inhibitors (CDK4/6i) and oncolytic viruses are promising therapeutic agents for the treatment of various cancers. As single agents, CDK4/6 inhibitors that are approved for the treatment of breast cancer in combination with endocrine therapy cause G1 cell cycle arrest, whereas adenoviruses induce progression into S-phase in infected cells as an integral part of the their life cycle. Both CDK4/6 inhibitors and adenovirus replication target the Retinoblastoma protein albeit for different purposes. Here we show that in combination CDK4/6 inhibitors potentiate the anti-tumor effect of the oncolytic adenovirus XVir-N-31 in bladder cancer and murine Ewing sarcoma xenograft models. This increase in oncolytic potency correlates with an increase in virus-producing cancer cells, enhanced viral genome replication, particle formation and consequently cancer cell killing. The molecular mechanism that regulates this response is fundamentally based on the reduction of Retinoblastoma protein expression levels by CDK4/6 inhibitors.
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