Replication stress results from obstacles to replication fork progression, including ongoing transcription, which can cause transcription–replication conflicts. Oncogenic signaling can promote global increases in transcription activity, also termed hypertranscription. Despite the widely accepted importance of oncogene-induced hypertranscription, its study remains neglected compared with other causes of replication stress and genomic instability in cancer. A growing number of recent studies are reporting that oncogenes, such as RAS, and targeted cancer treatments, such as bromodomain and extraterminal motif (BET) bromodomain inhibitors, increase global transcription, leading to R-loop accumulation, transcription–replication conflicts, and the activation of replication stress responses. Here we discuss our mechanistic understanding of hypertranscription-induced replication stress and the resulting cellular responses, in the context of oncogenes and targeted cancer therapies.

复制压力是由复制叉进程的障碍引起的，包括正在进行的转录，这可能导致转录-复制冲突。致癌信号可以促进转录活性的全球增加，也称为超转录。尽管癌基因诱导的超转录的重要性被广泛接受，但与癌症中复制压力和基因组不稳定性的其他原因相比，它的研究仍然被忽视。最近越来越多的研究报告称，致癌基因（如 RAS）和靶向癌症治疗（如溴结构域和末端外基序 (BET) 溴结构域抑制剂）会增加整体转录，导致 R 环积累、转录-复制冲突和激活复制应激反应。