New Target May Improve Glioblastoma Treatment Development

Aurintricarboxylic acid blocks the spread of glioblastoma.

A chemical compound may improve the development of new treatments for glioblastoma, according to a study published in Oncotarget.

“The findings of this study could represent a breakthrough in our efforts to find an effective long-term treatment against glioblastoma multiforme,” said lead author Dr Harshil Dhruv.

Current treatments for glioblastoma consist of surgery, radiation, and chemotherapy with temozolomide (TMZ). However, glioblastoma’s tendency to invade adjacent brain tissue prevents the surgical removal of all tumor cells. Additionally, glioblastoma cells can become resistant to TMZ, resulting in recurrence and patient death, often within 1 year.

Prior studies have identified how the binding of molecules TWEAK and Fn14 stimulate the migration of glioblastoma cells to invade and survive in healthy brain tissue. In the new study, the investigators found that the chemical compound aurintricarboxylic acid (ATA) suppressed the TWEAK-Fn14 cellular pathway, causing the cancerous cells to become more vulnerable to treatment.

The investigators identified ATA by screening pharmacologically active compounds for their ability to suppress TWEAK-Fn14 signaling. According to the authors, ATA provides a great starting point for developing new therapeutic agents for glioblastoma.

“These data demonstrate that ATA presents a scaffold structure that could be modified in ways to improve its properties and to develop as a potential therapeutic agent to limit invasion and enhance chemotherapeutic drug efficacy in [glioblastoma],” said senior and corresponding author Dr Nhan Tran.

The median survival of patients with glioblastoma is only 15 months, and survival statistics have not significantly improved over the past 3 decades. More than 16,000 Americans die each year of brain and other nervous system cancers.

“We simply must find a better way of treating patients with glioblastoma,” said co-author Dr Michael Berens, director of Translational Genomics Research Institute. “Identifying ATA could bring real hope to these patients by disrupting the cellular pathways that drive glioblastoma and make it such a formidable threat.”

In the future, the investigators will focus on identifying specific cellular signatures that indicate vulnerability to ATA. Additionally, they hope to use the ATA chemical structure to test modifications that would become drugs that could improve glioblastoma treatments.