New research offers hope to those affected by aggressive brain cancer

New research from the University of Sussex holds promise for extending life expectancy and enhancing treatment options for a common and aggressive brain cancer affecting thousands in the UK annually and hundreds of thousands globally.

Published in the Journal of Advanced Science, the study revealed that the protein PANK4, previously overlooked, can hinder cancer cells' response to chemotherapy in glioblastoma, an aggressive form of brain cancer and if the protein is removed, cancer cells respond better to the main chemotherapy drug used globally for the treatment of glioblastoma.

Glioblastoma stands as one of the most aggressive types of brain cancer, with approximately 3,200 adults diagnosed annually in the UK and around 250,000 to 300,000 cases globally. Despite treatment with surgery, radiation, and the chemotherapy drug temozolomide, which initially yields positive responses, patients typically face a bleak prognosis, with a survival rate of just one to 18 months post-diagnosis due to the rapid development of resistance in cancer cells.

"Glioblastoma is a devastating brain cancer, and researchers are working hard to identify ways to delay progression of the disease, and tackle cell resistance to treatment. As this is the first time that PANK4 has been linked to glioblastoma, the next step is to develop a drug targeting this protein to try to reverse chemo-resistance and restore sensitivity, ensuring that patients receive the best treatment and have better outcomes," explains Georgios Giamas, Professor of Cancer Cell Signalling at the University of Sussex.

The researchers identified the PANK4 protein, whose removal from cancer cells triggers cell death and enhances patients' response to temozolomide. Additionally, they observed that patients with elevated PANK4 levels experienced lower survival rates.

"There are a multitude of under-investigated proteins that may hold great potential for therapeutic intervention. Our study sheds light on this understudied protein, PANK4, unveiling a protective role in temozolomide-resistant cancer cells. Ultimately, PANK4 depletion represents a vulnerability that can now be exploited to restore sensitivity to the drug and improve treatment." said Dr Viviana Vella, research fellow at the University of Sussex.

The study's findings contribute to a groundbreaking body of research by the Sussex Scientists, dedicated to advancing early diagnosis and treatment of glioblastoma to develop a drug to counter chemo-resistance, offering improved prospects for patients battling the disease.

Reference: Viviana Vella, Angeliki Ditsiou, Anna Chalari, Murat Eravci, Sarah K. Wooller, Teresa Gagliano, Cecilia Bani, Emanuela Kerschbamer, Christos Karakostas, Bin Xu, Yongchang Zhang, Frances M.G. Pearl, Gianluca Lopez, Ling Peng, Justin Stebbing, Apostolos Klinakis, Georgios Giamas. Kinome‐Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma. Advanced Science, 2024; DOI: 10.1002/advs.202306027