A New Drug for GBM « Charlie Teo Foundation

A New Drug for GBM

Researcher name: Dr Alan Wang
Institution: MD Anderson Cancer Centre, U.S. and Pharmaxis, AUS
Grant name: Better Tools Grant
Grant amount: Up to $186K
Grant years: 2021-2022

Meet the Researcher

Dr Y. Alan Wang is a cancer biologist at one of the most prestigious comprehensive cancer centers in the U.S., MD Anderson. He trained at Harvard Medical School and his team has been responsible for identifying the cause of some types of cancers.

Brain cancer has only had 5 FDA approved treatments in the past 35 years, while some cancers have around 34, like breast cancer! We desperately need to trial more treatment options for brain cancer patients.

If the work from this project shows that this novel drug works to make the brain cancer more susceptible to attack by the immune system and extends survival in these preclinical brain cancer models, then this is the necessary data needed to get the drug into a Phase I clinical trial.

Evaluation of Pharmaxis LOX inhibitor in recurrent GBM

Glioblastoma (GBM) is the most common and lethal primary brain cancer with limited therapeutic option. Surgery and radiation are the two most common therapeutics for these patients and recurrences following these interventions almost always occur leading to a dismal 5-year survival rate of less than 5 %. Targeted therapeutic approaches on disease drivers have also generated limited success due to a lack of blood brain barrier penetrating drugs and tumour cells often develop resistance mechanisms to targeted therapy. In the past decade, our lab has been focused on the tumour microenvironment, composed mostly of tumour infiltrating macrophages in GBM. We have shown recently that PTEN (a tumour suppressor frequently lost in GBM) deficiency induced specific macrophage recruitment and we have provided concrete evidence that macrophage recruitment is largely due to the production of LOX by tumour cells. We demonstrated that inhibition of LOX at pharmacological and genetic levels can significantly extend survival of GBM-bearing animals. Immunotherapy has failed in GBM patients due, at least in part, to PTEN deficiency, and the fact that PTEN deficiency dependent infiltration of macrophage acting as an immune suppression mechanism and recurrent GBMs are often infiltrated with macrophages, we propose to test whether LOX inhibitor can significantly prevent GBM recurrence in patients undergoing surgery and chemoradiation therapy. In collaboration with Pharmaxis, we will test whether the LOX inhibitor PXS-5505, which has already shown safety profile in the phase 1 trials, would inhibit LOX mediated macrophage migration in tumour model in vivo, block GBM recurrence in GBM animal models, and synergize with immuno-checkpoint inhibitors to cure GBM in animal models.