CDK4/6 inhibitors, which are already FDA approved for the treatment of other forms of cancer, show early signs of promise in the treatment of a subtype of pediatric high-grade glioma, according to new research from Dana-Farber Cancer Institute and the Institute of Cancer Research in London.
Dana-Farber Cancer InstituteSep 3 2024 Treatment of a patient with a second relapse of this glioma subtype and no other treatment options resulted in 18 months of progression-free survival.
Filbin and her team discovered, surprisingly, that the tumor cells more closely resemble neurons. The team made this discovery using single cell multi-omic sequencing – the analysis of the active genes and proteins in individual cells in the tumor samples. The screen's results also pointed to CDK6 as a key vulnerability. CDK6 is a gene that regulates the cell division cycle and is important in cell fate decisions as cells differentiate. Several CDK4/6 inhibitors are already approved for the treatment of other cancers such as breast cancer.
The team first confirmed that three CDK4/6 inhibitors, ribociclib, palbociclib, and abemaciclib, could penetrate the blood brain barrier. Ribociclib, however, had several advantages, including being better tolerated at higher concentrations and more specificity to CDK6. In mouse models with patient-derived xenografts, treatment with ribociclib slowed tumor growth and extended survival.
Adolescents Blood Brain Brain Cancer Brain Tumor Cancer Cell Children CRISPR Drugs Genes Gliomas Hospital Leukemia Neuron Neurons Neuro-Oncology Oncology Research Tumor
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