{"id":31300,"date":"2024-06-21T17:11:19","date_gmt":"2024-06-21T15:11:19","guid":{"rendered":"https:\/\/imagineformargo.org\/?p=31300"},"modified":"2024-08-19T17:25:31","modified_gmt":"2024-08-19T15:25:31","slug":"molecular-analysis-and-testing-of-new-treatments-for-diffuse-midline-gliomas","status":"publish","type":"post","link":"https:\/\/imagineformargo.org\/en\/molecular-analysis-and-testing-of-new-treatments-for-diffuse-midline-gliomas\/","title":{"rendered":"Molecular Analysis and Testing of New Treatments for Diffuse Midline Gliomas"},"content":{"rendered":"

\"gliomes\"<\/p>\n

Diffuse Midline Gliomas in Children<\/strong><\/h2>\n

Pediatric brain tumors<\/a> are the leading cause of cancer-related mortality in children. Diffuse midline gliomas are the most common and severe form of malignant gliomas in children and adolescents (between 50 and 100 new cases are expected each year in France). Most affected children die within two years of diagnosis.<\/p>\n

Unfortunately, for these conditions, surgery is not an option, and radiotherapy remains the standard treatment, though its effectiveness is limited. Until the BIOMEDE trial, attempts to improve patient survival through chemotherapy or targeted therapies were unsuccessful. Thanks to the work of Dr. Jacques Grill and his team, co-funded by Imagine for Margo, our understanding of molecular alterations in gliomas has significantly advanced, notably through comprehensive molecular profiling of tumors in a vast majority of patients included in BIOMEDE. The data obtained has revealed the existence of targetable mutations, finally enabling the development of effective precision medicine that can be combined with radiotherapy.<\/p>\n

About the Project<\/strong><\/h2>\n

The WHO classification has recently grouped these gliomas, with the most emblematic pediatric form being the diffuse intrinsic pontine glioma. This grouping was made possible by identifying a common biological anomaly (H3K27M), which prevents tumor cell differentiation, keeping them in a stem cell state, allowing them to resist treatment and disseminate within the central nervous system.<\/p>\n

In addition to the H3K27M mutation, other anomalies may alter tumor behavior. Researchers have identified a subgroup of these diffuse midline gliomas that activate a specific signaling pathway (MAP kinases via BRAF or FGFR1 mutations). This subtype of diffuse midline glioma is less aggressive than the classic forms, and some patients survive more than five years after diagnosis (see the article on BIOMEDE<\/a>). By comparing the gene expression profiles of these specific gliomas, Dr. David Castel’s team has identified the activation of other pathways, such as mTOR and senescence. While the mTOR pathway allows cells to survive therapeutic stress, the senescence pathway allows cells to resist treatment by remaining dormant, only to proliferate later.<\/p>\n

Dr. Castel’s team believes it is crucial to understand how this second line of mutation (BRAF or FGFR1) interferes with the oncogenic process in cells with the initial H3K27M alteration. This knowledge could lead to the development of new treatments targeting these various alterations, representing up to 20% of these gliomas.<\/p>\n

In this project, researchers first aim to understand the genetic factors and microenvironment of these tumors. Then, they develop cellular and murine models to investigate the biology of these particular tumors and their response to promising therapeutic avenues (senescence treatment with BCL2 inhibitors, mTOR pathway treatment with everolimus, treatment directly targeting BRAF or FGFR1 mutations). These results will be complemented by analyzing the efficacy of ONC201 and 206, with 201 currently being tested in the BIOMEDE 2 trial.<\/p>\n

Researchers involved in this project hope that, with this dual approach, significant progress can be made in curing this disease.<\/p>\n

Trial Follow-Up:<\/strong><\/h2>\n

Start Date:<\/strong> 2024<\/p>\n

Project Summary:<\/strong><\/h3>\n