A novel treatment for glioblastoma, the most aggressive type of brain cancer, has shown remarkable promise in early trials, boosting the prospect of extending survival rates beyond the current average of 18 months.

Scientists are looking into Targeted Alpha Therapy (TAT) as a new technique to treat glioblastoma. This malignancy has perplexed scientists for decades, since it spreads quickly and resists current treatments.

Currently, the conventional treatment for GB comprises surgery, radiation, and the chemotherapeutic medication temozolomide. However, the five-year survival rate is less than 5–10%, so experts are searching for better alternatives.

Scientists at the University of South Australia (UniSA) are evaluating TAT and other studies to determine if it can help treat recurrent glioblastoma.

A recent publication in Targeted Oncology features a discussion on the advantages of TAT by UniSA PhD candidate Maram El Sabri, medical radiation physicist Professor Eva Bezak, and oncologist Professor Frank Saran.

"Unlike external beam radiotherapy, which delivers radiation more diffusely over a larger volume, TAT delivers high amounts of lethal radiation to the tumour at very short range, hitting its target without significantly affecting surrounding healthy tissue," Maram adds.

"Alpha particles are up to 10 times more potent when compared to standard photon radiation therapy, killing the cancer cells or at the very least slowing their future growth by damaging their DNA."

Glioblastomas spread swiftly and mingle with normal brain tissue, making them difficult to target with radiation.

Animal studies demonstrate that few medicines can pass the blood-brain barrier and reach malignancy. When they do, they often cause harm to healthy tissue.

In pre-clinical trials, TAT raised survival rates by 16.1% in new glioblastoma patients and 36.4% in recurrent cases. The studies also reveal that it has few adverse effects.

Professor Bezak notes that Australian scientist Professor Barry Allen, who passed away from cancer in 2019, first proposed TAT as a cancer therapy more than 20 years ago. "He was ahead of his time." She explains that it has taken a long time for clinicians to gradually adopt TAT and conduct animal (pre-clinical) and human (clinical) investigations.

"Pre-clinical studies yield really promising outcomes. External beam radiation uses alpha emitters, which are up to ten times more harmful to cells than gamma radiation. In addition, targeted alpha treatment is less expensive than current immunotherapy or molecular targeting medications.

Professor Saran, an adjunct clinical professor at UniSA and an experienced radiation oncologist, highlights the lack of progress in treating glioblastoma in recent decades, which has reignited interest in TAT. "The most exciting development was the discovery of the chemotherapy drug temozolomide in the 1980s, but that has only improved the expected median survival by around three months," adds the researcher.

"Research in this field is quite limited for a variety of reasons. For starters, glioblastoma is an uncommon malignancy that affects a small proportion of the population. It also has extremely low survival rates, and there is a long history of failed research in this field. Unfortunately, pharmaceutical corporations are typically hesitant to engage in GB since it has a low success rate and is not commercially viable."

As part of her PhD research, Maram is developing a model to determine the best approach to delivering TAT to the brain after surgery in conjunction with traditional treatments. "I'm curious to see if we can identify the optimal dose and radiation range by combining TAT with conventional treatment approaches. "If this works, we could see some significant results in terms of extending a patient's life," she says.