Proceedings from the 4th Memorial Alicia Pueyo Workshop: “Moving Towards a Cure for Diffuse Intrinsic Pontine Glioma”

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Background

Diffuse Intrinsic Pontine Glioma (DIPG) is a devastating and incurable children’s brain tumor. In 2006, Alicia (age 6) was diagnosed with DIPG. Impossible to remove by surgery, and with no effective treatments except for palliative radiotherapy to gain a few more months, there is no cure. Life expectancy remains about 12-18 months. Alicia didn’t break the odds and after 15 months of fighting, she succumbed to the disease in November of 2007. Afterwards, the family, like many others who had gone through this nightmare, became strongly committed to fighting this disease to find a cure. The Alicia Pueyo Fund was set up in 2008 at Sant Joan de Déu Hospital to provide support and information to affected families and facilitating international researchers’ collaboration. The challenge was up to those willing to change minds, think out of the box and walk new paths to cure DIPG. The first International Workshop on DIPG (the first Memorial Alicia Pueyo meeting) took place in Barcelona on February 26, 2009. Afterwards, the international network of families prompted subsequent meetings in Toronto, Cincinnati, and Amsterdam. The second Memorial Alicia Pueyo meeting took place on February 26, 2012. The DIPG networks grew stronger in the US and Europe and International registries were set up. The Alicia Pueyo’s Fund focused on supporting the Hospital Sant Joan de Déu research group.

In 2012, with the invaluable collaboration of the Necker Institute, the first patient was sent from Barcelona to Paris for biopsy. Since April 2013, biopsy is a standard procedure for DIPG patients at Hospital Sant Joan de Déu. The availability of tissue samples for research brought a completely different scenario. Researchers identified DIPG mutations and understood why treatments failed. DIPG was defined as a biological entity by itself, different from any other adult or pediatric brain tumor. The 2016 WHO classification of brain tumors recognized the entity as midline gliomas with H3K27M. Robust mouse models of DIPG, several cell lines and tools that have accelerated enormously the development of novel drugs and delivery methods were rapidly developed. The fantastic acceleration of DIPG knowledge was discussed at the third Memorial Alicia Pueyo Workshop (February 26, 2015). New clinical trials incorporating biological biomarkers were presented. The international researchers’ networks have since produced several outstanding papers on the cellular origin of DIPG, the epigenome derived from the Histone H3 founding mutation and the vascular and immune microenvironment characteristic of DIPG.

Current knowledge, international alliance, laboratory models and dedicated clinical trials were unthinkable when Alicia was diagnosed. The extraordinary commitment of affected families and the coordinated work of clinicians and researchers willing to change minds have prompted revolutionary advances to find a cure for DIPG. The 4th Alicia Pueyo International Workshop is set for February 26-27, 2018. The meeting presentations are summarized in this Research Topic collection. Section 1 covers different aspects of cell of origin, structure and microenvironment. Section 2 describes the current DIPG management and ongoing clinical Trials, and Section 3 explores the many novel targets being investigated in the laboratories worldwide.

Keywords: Pontine glioma of childhood, DIPG, pediatric brain tumor, Alicia Pueyo Fund, H3K27M brainstem tumors, Hospital Sant Joan de Déu Barcelona

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