CDK7-dependent transcriptional addiction in bone and soft tissue sarcomas: Present and Future

Cancer arises from genetic alterations that invariably contribute to dysregulated transcriptional programs. These dysregulated programs establish and maintain specific cancer cell states, leading to an intensive dependence on a set of certain regulators of gene expression. The CDK7 functions as the core of transcription, and governs RNA polymerase II and the downstream oncogenes expression in cancers. CDK7 inhibition leads to reduced recruitment of super-enhancers-driven oncogenic transcription factors, and the depression of these associated oncogenes expression, which indicates the dependence of transcriptional addiction of cancers on CDK7. Given that specified oncoproteins of sarcomas commonly function at oncogenic transcription, targeting CDK7-denpendent transcriptional addiction may be of guiding significance for the treatment of sarcomas. In this review, we summarize the advances in mechanism of targeted CDK7-dependent transcriptional addiction and discuss the path ahead to potential application discovery in bone and soft tissue sarcomas, providing theoretical considerations for bio-orthogonal therapeutic strategies.