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Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than one year. One of the primary reasons this disease is so deadly is because DIPG cells respond well to stress, making them difficult to kill with radiation alone.

Marta Alonso

In a recent interview with Dr. Marta Alonso of the University Hospital of Navarra, who was awarded a ChadTough Defeat DIPG Game Changer Grant in 2020, we learned more about her findings while studying the effects of oncolytic immunotherapy to treat patients with DIPG.

Her project explores the use of the oncolytic virus DNX-2401 (a type of virus that breaks down cancer cells, leaving normal cells intact) in combination with radiotherapy to attack the tumor in newly diagnosed DIPG patients.

CTDDF: Can you tell us a bit about yourself and how you decided to work in the world of brain cancer research?

Dr. Marta Alonso: I grew up in a small village in the north of Spain close to the Pyrinees, and during high school I knew I wanted to do something with cancer research. After completing my PhD in Health Sciences in Pamplona (Spain), I moved to the States to continue my training. I started to work in the field of adult brain tumors during my postdoc at MD Anderson in the lab of Drs. Fueyo and Gomez-Manzano. These superb mentors taught me a lot. There, I discovered how much still needed to be accomplished in this field. Later on, I was very lucky to receive a fellowship grant from the American Brain Tumor Association that was supported by a family whose child had a medulloblastoma. After meeting the family, I decided that, when I got my own lab, I would devote my research effort to the field of pediatric brain tumors.

CTDDF: ChadTough Defeat DIPG recently supported your work on oncolytic immunotherapy. It’s been fascinating to learn that a virus could potentially kill cancer cells. Can you explain how that works and what you have discovered thus far?

Dr. Marta Alonso: Viruses are biological agents that we can use to our advantage. Our research has shown that it is possible to inject viruses into the brainstem without much complications. Kids were home 2-3 days after the procedure, and the therapy was well tolerated, with few secondary effects such as fever and flu-like symptoms. Additionally, we have seen that the virus is doing something in terms of efficacy, but the research is still in a very early phase to be super optimistic. Clearly, there is an antitumor effect there that can be improved upon while keeping safety top of mind. We want to keep investing in that.

CCDDF: What kind of impact do you hope your research will have on DIPG?

Dr. Marta Alonso: We are hopeful that this research will provide an avenue to improve the quality of life and outcome for DIPG patients. We’ve shown that oncolytic viruses are safe and display a degree of efficacy, and I believe our research has uncovered them as a realistic therapeutic option that now needs to be refined. I believe more researchers will look into this therapy now and improve upon it.

CCDDF: This project was supported by a ChadTough Defeat DIPG Game Changer Grant. What do you feel is the importance of private funding in moving the field of DIPG forward?

Dr. Marta Alonso: I believe private funding serves at different levels. It definitely fills a gap that government funding is not reaching, but at the same time it has created a momentum and awareness to the general public that I believe, in turn, will spark more public investment in this field. On the other hand, for researchers, private funding provides us with a deep feeling of responsibility towards the families and society in general and a great deal of motivation to change the course of these tumors.

CCDDF: Can you comment on the current state of DIPG treatment in general? For example, how have things changed since Chad Carr and Michael Mosier were diagnosed in 2014?

Dr. Marta Alonso: I believe the field has undergone a great transformation in the last several years. We have gone from knowing very little about DIPG tumors to understanding them, thanks to biopsies and the great seminal work of several scientists that have opened the door for real change in how we approach the disease. Now we have more options besides radiotherapy and conventional chemotherapy. Clinical research is advancing really quickly and discovering drugs that specifically target these tumors. We still have a lot of work to do, but things are moving, and I’m confident we will one day see a breakthrough in the fight against DIPG.

To learn more about this study, visit https://www.nejm.org/doi/full/10.1056/NEJMoa2202028