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DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition
… Continue Reading: DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial InhibitionIzquierdo et al., 2022, Cancer Discov. DOI: 10.1158/2159-8290.CD-20-0930 Mitogen-activated protein kinase (MAPK) pathway alterations are commonly found in childhood cancer, particularly brain tumors, and especially low- and high-grade gliomas. Although targeted agents against the MAPK pathway (inhibitors targeting BRAF – vemurafenib, dabrafenib and MEK – trametinib, selumetinib, cobimetinib) have become…
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Targeting the multifaceted BRAF in cancer: New directions
… Continue Reading: Targeting the multifaceted BRAF in cancer: New directionsToye et al., 2024. Oncotarget. DOI: 10.18632/oncotarget.28612. PMID: 39018217 MAPK activation predominantly occurs through genomic alterations in RAS and BRAF. BRAF is an effector kinase that functions downstream of RAS and propagates this oncogenic activity through MEK and ERK. Across cancers, BRAF alterations include gain of function mutations, copy number…
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Effective targeting of PDGFRA-altered high-grade glioma with Avapritinib
… Continue Reading: Effective targeting of PDGFRA-altered high-grade glioma with Avapritinib(Lisa Mayr et al., 2025. Cancer Cell. DOI: 10.1016/j.ccell.2025.02.018. PMID: 40086436) [Discussion] Recent collective sequencing efforts have identified several key molecular drivers of pediatric and young adult patients diagnosed with HGG or DMG. Among them, PDGFRA has emerged as a promising therapeutic target due to its frequent genomic alterations and…
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An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma
… Continue Reading: An Integrative Model of Cellular States, Plasticity, and Genetics for GlioblastomaNeftel et al., 2019, Cell I believe the 2019 paper by Neftel et al. is one of the most significant journals not only in terms of glioblastoma (GBM), but more importantly, as a broader paradigm for understanding cellular heterogeneity and plasticity in cancer. The study highlights the power of single-cell…
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Collaboration with M4K Pharma
… Continue Reading: Collaboration with M4K PharmaM4K Pharma, founded by Aled Edwards and Owen Roberts from University of Toronto, is an open source pharmaceutical company dedicated to accelerating drug discovery and development for rare childhood cancers (e.g. DIPG) through public data-sharing and effective collaboration. Since it is unique for a pharmaceutical company to share their thoughts/on-going…
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ALK2 Inhibitors Display Beneficial Effects in Preclinical Models of ACVR1 mutant Diffuse Intrinsic Pontine Glioma
… Continue Reading: ALK2 Inhibitors Display Beneficial Effects in Preclinical Models of ACVR1 mutant Diffuse Intrinsic Pontine GliomaThis paper identifies the two physicochemically attractive LDN compounds, the most potent LDN193189 and selective LDN214117, as promising lead compounds with efficient inhibition of proliferation and induction of apoptosis in vitro. Additionally, enhanced survival of mice bearing orthotopic ACVR1-mutant patient-derived DIPG xenografts in vivo along with good pharmacokinetics and CNS…
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Recent Advances in ALK2 Inhibitors
… Continue Reading: Recent Advances in ALK2 InhibitorsOver the past few years, a greater diversity of chemotypes of ALK2 inhibitors have emerged. Some compounds had higher selectivity and those were modulated to ensure oral bioavailability and CNS penetration.
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Diffuse Intrinsic Pontine Glioma (DIPG)
… Continue Reading: Diffuse Intrinsic Pontine Glioma (DIPG)Within the K27M altered tumors, one of my main interest lies on a specific tumor type called Diffuse Intrinsic Pontine Glioma (DIPG). DIPG is a rare, aggressive, and malignant brain tumor which develops in a part of the brainstem called the pons and more than 80% of DIPG patients are…
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Pediatric high-grade glioma: biologically and clinically in need of new thinking
… Continue Reading: Pediatric high-grade glioma: biologically and clinically in need of new thinkingJones et al., 2017, Neuro-Oncology Below are my notes for this paper!
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The World Health Organisation (WHO) Classification of the Central Nervous System
… Continue Reading: The World Health Organisation (WHO) Classification of the Central Nervous SystemPublished in 2021, the fifth edition of the WHO Classification of Tumors of the Central Nervous System highlights the role of advances in novel molecular profiling approaches in identifying new CNS tumor types and subtypes. The changes in CNS tumor classification have been impacted by the improvements in novel diagnostic…
