Highlights in this article
Glioblastoma is an aggressive type of cancer that occurs in the brain or spinal cord. Due to the lack of effective treatments, the prognosis is very poor. In this article, Dr. Mills’s group in Cold Spring Harbor Laboratory identified novel mechanisms where glioblastoma is developed. Thus, targeting this novel mechanism resulted in glioblastoma tumor suppression. This research provides a potential strategy to treat glioblastoma with a small molecule inhibitor targeting this novel mechanism, which has already been developed. The launch and success of clinical trials in treating glioblastoma using this small molecule inhibitor will be expected.
Background
Glioblastoma (GBM) is the most aggressive and fatal form of brain cancer in adults. It’s characterized by rapid growth, diffuse infiltration and resistance to therapy. Despite significant progress in understanding the underlying biology of the disease, the median survival for GBM patients is only 14.6 months with standard therapy which includes surgical resection followed by radiation and temozolomide chemotherapy.
Recently, the development of new therapeutic options such as immunotherapy, targeted therapy and the use of oncolytic viruses has shown promising results in clinical trials. For example, immunotherapy using drugs such as pembrolizumab and nivolumab targeting PD-1 has been approved for the treatment of GBM. Targeted therapies such as bevacizumab and cediranib, which target the blood vessels that feed the tumor, have also been found to improve survival in GBM patients. Additionally, the use of oncolytic viruses, which are genetically engineered to specifically target and destroy cancer cells, is also being explored as a potential treatment option for GBM. However, there is still a lot of work to be done in terms of identifying new therapeutic targets and developing more effective treatment options for GBM patients.
Discovery
Glioblastoma (GBM) is the most common and deadly form of brain cancer in adults, but it’s unclear how GBM develops in people with normal functions of tumor suppressor gene p53, the most frequently mutated gene in cancer. In this study, Dr. Mills’s group discovered a specific mechanism in GBM where a protein called BRD8 helps maintain a certain structure on the DNA that blocks the activity of p53. This allows the cancer cells to continue growing. The study also found that targeting BRD8 with certain drugs could restore p53’s tumor-suppressing function and potentially be a new treatment option for GBM patients who have normal functions of the p53 gene.
For more information:
Nature 2022 12/21
https://www.nature.com/articles/s41586-022-05551-x
BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network
Dr. Alea A. Mills’s website: