High-grade glioma (HGG), a type of aggressive brain cancer, accounts for the leading cause of cancer-related mortality for children and adolescents. These cancers lack a therapeutic target, reducing viable treatment options. A recent study in Cancer Cell has determined upregulation of a protein called CDK6 occurs in cells involved in the development of certain types of gliomas.
The study examined glioma cells, finding them sensitive to drugs that inhibit CDK signaling. In addition, using preclinical mouse models, the researchers showed that glioma cells reacted to a drug that degraded CDK6. Treatment with a CDK6-specific degrader significantly slowed tumor growth and prolonged survival in glioma-bearing mice.
The report also discusses a case study in which a patient with progressive HGG received ribociclib, a CDK6 inhibitor approved for the treatment of certain types of advanced breast cancer (hormone-receptor positive, HER2-negative). The patient, a ten-year-old girl, had a grade 4 HGG with mutations consistent with the CDK6-sensitive preclinical findings. Initially, the patient responded to radiation and chemotherapy but experienced a recurrence 13 months later. The patient did not respond favorably to second-line chemotherapy. On a compassionate-use basis, doctors treated the patient with third-line ribociclib. The patient has remained asymptomatic, and she even returned to attending school full-time.
The patient experienced 17 months of progression-free survival following ribociclib treatment. At the time of writing, the researchers reported that the patient was being considered for additional treatment.
The authors conclude that the preclinical and clinical data collected from their translational approach demonstrates both tolerability and efficacy of ribociclib for HGG. The study encourages further research to validate the safety and effectiveness of CDK6 inhibitory treatment approaches in clinical trials. Together, the data presented in the study strongly implement CDK6 as a promising druggable target which could help make significant advances in the treatment of aggressive brain cancers in children.
Sources: Neuro Oncol, Cancer Cell