Formulation breakthrough enables new treatment for Glioblastoma multiforme


Glioblastoma multiforme (GBM), also known as Grade IV astrocytoma, is the most aggressive form of brain cancer. The severity of this cancer is high and the median overall survival is 1-2 years.1 The lack of effective therapies is mainly due to the inability of drugs to reach effective concentrations within the brain. The only targeted agent approved for recurrent GBM patients is Roche’s Avastin (bevacizumab), approved in the United States in 2008. Otherwise, the best option remains generic chemotherapeutic agents in combination with radiotherapy. Better treatments for GBM are sorely needed.

Cancer biologists recently uncovered a new drug target, STAT3, which plays an important role in the tumorigenesis of many cancer types, including GBM.2,3,4 The small molecule atovaquone has been shown to be a potent STAT3 inhibitor, and  atovaquone works synergistically with radiotherapy to inhibit tumor growth.5,6 Atovaquone is a poorly water-soluble compound which is currently approved for use as an antifungal agent. Unfortunately, all available formulations of atovaquone cannot deliver a high enough dose to the brain. In order to achieve therapeutically effective concentrations to the brain, a new formulation approach is needed.

Amorphous solid dispersions (ASDs) present a promising formulation strategy for improving the bioavailability of poorly soluble drugs. Unfortunately, none of the established techniques for forming ASDs are able to achieve adequate bioavailability of atovaquone for treating brain cancers. The Williams Lab at UT Austin has overcome this obstacle by incorporating a spontaneously emulsifying component (SEC) into the thermal processing step with polymeric carrier and drug. The resulting novel atovaquone formulation exhibits ideal properties for bioavailability such as high absorption, rapid disintegration, and dispersion into fine particles in an aqueous environment. These improved properties makes it possible to achieve therapeutically effective brain levels of atovaquone. Proof-of-concept results in mice provides promise for this new atovaquone formulation to be used an improved treatment for GBM.2


1.  GlobalData, Report Code: GDHC090POA, October 2018

2.  Takabe, H. et al., Pharmaceutics. 2018 Jun; 10(2): 60.

3.  Luwor R.B. et al.,  J. Clin. Neurosci. 2013;20:907–911.

4.  Villalva C. et al.,  Int. J. Cancer. 2011;128:826–838.

5.  Coates, J.T.T. et al., Cell Death Discov. 6, 110 (2020).

6.  Ashton T.M et al., Nat. Commun. 2016;7:12308.