Publications by authors named "Andria Rakotomalala"
Article Synopsis
- - Pediatric diffuse midline gliomas (pDMG) are aggressive childhood cancers characterized by fatal outcomes and linked to specific genetic mutations, particularly K27M in histone H3.
- - About 20 to 30% of these tumors have alterations in the BMP signaling pathway, specifically involving mutations in the BMP type I receptor ALK2, but the effects of BMP in non-mutated cases are not fully understood.
- - Recent research reveals that BMP2 and BMP7 are active in both wild-type and mutant tumors, and they work with the K27M mutation to alter cell behavior, indicating that the BMP pathway could be a target for treatment in pDMG.
Article Synopsis
- Diffuse midline gliomas (DMG), particularly diffuse intrinsic pontine gliomas (DIPG), are highly lethal childhood cancers, with palliative radiotherapy offering limited survival benefits of 9-11 months.
- ONC201, a drug that targets certain pathways in cancer cells, has shown potential effectiveness against DMG, but further research is needed to understand how different genetic mutations affect its response.
- Studies indicate that DIPGs with PIK3CA mutations are more sensitive to ONC201, while those with TP53 mutations are resistant; combining ONC201 with the drug paxalisib can enhance treatment effectiveness by overcoming metabolic adaptations linked to these mutations.
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG.
View Article and Find Full Text PDFHigh-grade gliomas represent the most lethal class of pediatric tumors, and their resistance to both radio- and chemotherapy is associated with a poor prognosis. Recurrent mutations affecting histone genes drive the tumorigenesis of some pediatric high-grade gliomas, and H3K27M mutations are notably characteristic of a subtype of gliomas called DMG (Diffuse Midline Gliomas). This dominant negative mutation impairs H3K27 trimethylation, leading to profound epigenetic modifications of genes expression.
View Article and Find Full Text PDFHypoxia in Solid Tumors: How Low Oxygenation Impacts the "Six Rs" of Radiotherapy.
Front Endocrinol (Lausanne)
February 2022
Radiotherapy is an important component of cancer treatment, with approximately 50% of all cancer patients receiving radiation therapy during their course of illness. Nevertheless, solid tumors frequently exhibit hypoxic areas, which can hinder therapies efficacy, especially radiotherapy one. Indeed, hypoxia impacts the six parameters governing the radiotherapy response, called the « six Rs of radiation biology » (for Radiosensitivity, Repair, Repopulation, Redistribution, Reoxygenation, and Reactivation of anti-tumor immune response), by inducing pleiotropic cellular adaptions, such as cell metabolism rewiring, epigenetic landscape remodeling, and cell death weakening, with significant clinical repercussions.
View Article and Find Full Text PDFPediatric brain cancers represent the most frequent solid tumors and the leading cause of cancer-driven mortality in children. Pediatric High Grade Gliomas display a very poor prognosis. Among these, DIPG (Diffuse Intrinsic Pontine Gliomas), localized to the brain stem, cannot benefit from a total exeresis due to this critical location and to their highly infiltrating nature.
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