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DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition
Izquierdo 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
Toye 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 alterations, and structural rearrangements.
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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
Dagogo-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
Martin-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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A new genomic framework to categorize pediatric acute myeloid leukemia
Umeda 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.
