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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 an important initial success story…
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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
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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 its essential role in driving…
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Tumour Heterogeneity and Resistance to Cancer Therapies
… Continue Reading: Tumour Heterogeneity and Resistance to Cancer TherapiesDagogo-Jack and Shaw, Nat Rev Clin Oncol 15, 81-94 (2018) One of the biggest challenges in precision oncology is the dynamic and multifaceted nature of tumour heterogeneity. Dagogo‑Jack and Shaw articulate how intra- and intertumoural heterogeneity drive resistance to targeted therapies, immunotherapies, and even cytotoxic agents.
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Liquid Biopsy – Priming Agents Transiently Reduce the Clearance of Cell-Free DNA to Improve Liquid Biopsies
… Continue Reading: Liquid Biopsy – Priming Agents Transiently Reduce the Clearance of Cell-Free DNA to Improve Liquid BiopsiesMartin-Alonso et al., 2024, Science 383, 274 During the course of my Master’s degree in Cancer Biology at Imperial College London, UK, one of the projects I have been working on was titled “Searching for oncogenic mutations in circulating tumor DNA (ctDNA) from gestational trophoblastic tumors (GTT)”. The rationale behind this project was to identify…
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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 transcriptomics in decoding the complexity…
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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 penetration raises the prospect of…
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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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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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A new genomic framework to categorize pediatric acute myeloid leukemia
… Continue Reading: A new genomic framework to categorize pediatric acute myeloid leukemiaUmeda et al., 2024, Nature Genetics. DOI: 10.1038/s41588-023-01640-3 Many pediatric-specific driver alterations are underrepresented in the current classification schemas. The study systemically categorized 887 pAML into 23 mutually distinct molecular categories. These included major entities covering 91.4% of the cohort, such as UBTF and BCL11B.
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