Three-Pronged Therapy: A New Treatment for Incurable Brain Tumours

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1. Please give a summary of your research.

On average sixteen hundred people are diagnosed with brain cancer in Australia every year. Approximately twelve hundred people die every year in Australia from brain cancer. These numbers are small compared to other cancers; consequently there has been no significant development in treatment methods over the past thirty years. However, it is no source of solace to a patient diagnosed with a brain cancer to lean that their form of cancer is rare.


My PhD research developed a new approach to selectively target malignant brain cancer cells. The treatment method combines three forms of attack. Firstly, an anticancer drug (methotrexate – MTX) is used that impairs the growth of cancer cells and reduces their ability to repair DNA damage. Secondly, a radiosensitiser drug (bromodeoxyuridine – BrUdR) is used. This makes the tumour cell more sensitive to radiation. Thirdly, X-rays are used. But not X-rays with any old energy! The X-ray energy is carefully chosen to optimise their interaction with the radiosensitiser.


The radiosensitiser maximises the delivery of lethal x-ray energies onto the cancer cells. Furthermore, the radiosensitiser minimises the number of healthy cells that are exposed to the toxic effects of radiation. After our deadly dose has been delivered, the anti-cancer drug impairs the ability of the cancer cells to recover from our attack.

I am currently translating this groundbreaking to pre-clinical evaluation in small animal models as the next step in developing this promising therapy for eventual clinical application.

2. Please include any additional details you would like to share

Cancer is the second largest cause of death in worldwide. In Australia, more than 80,000 people develop cancer every year. Despite significant advances in surgery, radiotherapy, and chemotherapy, 40% of patients fail to survive long term. The treatment of brain cancers is particularly problematic. Gliomas are among the most frequently found primary brain tumours. The treatment of high-grade gliomas poses a major challenge as they are resistant to radiotherapy and chemotherapy often fails because of inadequate drug delivery inside the tumour. In fact, there has been no improvement in treatment in the past 30 years. A new effective method to treat high-grade glioma is desperately needed.

 

My research highlights the importance of linking drug activation to precise targeting of optimised energy x-ray beams [1]. I revealed a synergy that is obtained by combining the MTX and BrUdR with X-rays tuned at optimum energy, the combined action of these three prongs more than doubled the death of glioma tumour cells compared to irradiation alone or with either drug and irradiation. I have established that the enhancement in glioma tumour cell killing activity is strongly dependent on the x-ray photon energy [2][3].

 

In Australia, the five-year survival rates for brain cancer are low compared to other cancers. To improve the control of local tumours and to reduce tumour recurrence improvements in two factors are required: there needs to be an improved delivery of radiation dose to the tumour and there needs to be more efficient killing of the cancer cells. My innovative therapy delivers both of these outcomes. The radiosensitiser ensures that more dose is delivered to the cancer. This, in turn, ensures that there is more efficient killing of the cancer cells. In fact, because of the improved targeting, it is possible to kill more cells than before whilst using a lower dose. My findings show a significant improvement in the treatment of gliomas. In the future patients can be treated with a lower dose than is currently the case, because the dose actually delivered to the tumour is higher.

 

References

[1] Oktaria S (2014) Advances in Targeted Radiosensitiser and Nanotherapeutic Agents for Cancer Therapy. Doctoral Dissertation Thesis. School of Physics. University of Wollongong. http://ro.uow.edu.au/theses/4268.

[2] Oktaria S, Corde S, Lerch ML, Konstantinov K, Rosenfeld AB, Tehei M (2015) Indirect radio-chemo-beta therapy: A targeted approach to increase biological efficiency of x-rays based on energy. Phys Med Biol 60:7847-7859. doi: 10.1088/0031-9155/60/20/7847.

[3] Three-pronged glioma shows promise – MedicalPhysicsWeb, November 2, 2015 (http://medicalphysicsweb.org/cws/article/research/63064).

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