A pioneering study has been released, showcasing the first-ever uncovering of the evolutionary dynamics of glioblastoma recurrence through proteogenomic analysis, offering potential therapeutic avenues.

The research team, led by Professor Jason K. Sa from Korea University College of Medicine's Department of Biomedical Informatics and Professor Jong Bae Park from the National Cancer Center, has elucidated the evolutionary process of glioblastoma recurrence through integrative proteogenomic analysis.

They have provided new treatment opportunities based on their findings, which are published in the journal Cancer Cell.

Glioblastoma is known for its complex genetic alterations and cellular capability to interact with surrounding neurones. It is particularly challenging due to its high recurrence rate and the prevalent resistance to standard treatments like chemotherapy and radiation therapy.

The research team meticulously analysed the genomic, transcriptomic, and proteomic profiles of matched primary and recurrent glioblastoma from 123 patients.

They discovered that The recurrent tumours have undergone neuronal transition through activation of the WNT/PCP signalling pathway and the BRAF protein kinase.

The study also illustrated, through experimental validation with patient-derived cells and animal models, that the formation of synapses between normal neurones with tumour cells constituted a critical role in the recurrent tumour's resistance to standard therapy.

Moreover, The research highlighted that administering vemurafenib, a BRAF-inhibiting targeted drug, with temozolomide, a conventional chemotherapy drug, effectively impaired the neuronal transition and invasive capacity of the recurrent tumour cells, significantly prolonging survival in animal models.

This outcome validates targeting the BRAF protein kinase as a novel strategy for combating recurrent glioblastoma, paving the way for innovative treatment opportunities.

Professor Sa stated, "The challenge with traditional genomic analysis was its inability to fully decipher the patterns of tumour evolution. This research, however, leverages a multidimensional data analysis approach, offering new therapeutic possibilities."

Professor Park explained, "This is the first time that we've been able to demonstrate, through the integration of genomic, proteomic, and clinical data, the role of neuron-brain tumour cell network formation in the recurrence of brain tumours."

Source: Korea University College of Medicine