Targeting CDK9 for the Treatment of Glioblastoma

Abstract

Simple Summary Inhibition of cyclin-dependent kinase 9 (CDK9) can impact multiple survival pathways in cancers and may be a promising therapeutic approach for glioblastoma, which is known to be highly resistant to treatments and thus challenging to treat. This review assesses the mechanisms by which CDK9 inhibition impacts cancer cell survival pathways in glioblastoma and other cancer types and presents results from clinical trials involving CDK9 inhibitors. A more thorough understanding of these mechanisms may lead to novel combination treatment strategies involving CDK9 inhibitors that can ultimately improve clinical outcomes for glioblastoma patients. Abstract Glioblastoma is the most common and aggressive primary malignant brain tumor, and more than two-thirds of patients with glioblastoma die within two years of diagnosis. The challenges of treating this disease mainly include genetic and microenvironmental features that often render the tumor resistant to treatments. Despite extensive research efforts, only a small number of drugs tested in clinical trials have become therapies for patients. Targeting cyclin-dependent kinase 9 (CDK9) is an emerging therapeutic approach that has the potential to overcome the challenges in glioblastoma management. Here, we discuss how CDK9 inhibition can impact transcription, metabolism, DNA damage repair, epigenetics, and the immune response to facilitate an anti-tumor response. Moreover, we discuss small-molecule inhibitors of CDK9 in clinical trials and future perspectives on the use of CDK9 inhibitors in treating patients with glioblastoma.