{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:08:12Z","timestamp":1788782892676,"version":"build-2803163510"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>BRAF V600E occurs in selected primary central nervous system (CNS) tumors and in a subset of thyroid cancers that can metastasize to the brain, but the shared alteration does not make these diseases biologically equivalent. This Mini Review examines programmed cell death evasion in pleomorphic xanthoastrocytoma and ganglioglioma, with selected molecular and clinical comparisons involving epithelioid glioblastoma, pilocytic astrocytoma, pediatric low-grade glioma, and thyroid cancer brain metastases (TCBM). Evidence linking BRAF\u2013MEK\u2013ERK signaling to apoptosis is strongest in non-CNS thyroid cancer and other BRAF-mutant models; direct validation in TCBM remains limited. Ferroptosis sensitization has been demonstrated preclinically in BRAF V600E anaplastic thyroid cancer outside the brain, whereas the ferroptosis suppressor protein 1 (FSP1)\/coenzyme Q10 (CoQ10) axis and dihydroorotate dehydrogenase (DHODH) remain general mechanistic frameworks rather than established dependencies in the target CNS settings. Clinical studies support BRAF\/MEK inhibition in BRAF V600E-mutant glioma and systemic anaplastic thyroid cancer, but direct TCBM intracranial evidence is restricted to very limited, confounded observations. The intact blood\u2013brain barrier, heterogeneous blood\u2013tumor barrier, efflux transporters, and brain microenvironment further complicate inference from systemic outcomes. We therefore separate direct, indirect, and hypothesis-generating evidence and identify disease-specific pharmacokinetic, mechanistic, and prospective clinical studies as priorities.<\/jats:p>","DOI":"10.3389\/fneur.2026.1921351","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:18:19Z","timestamp":1788779899000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Programmed cell death evasion in BRAF V600E-driven primary CNS tumors and thyroid cancer brain metastases"],"prefix":"10.3389","volume":"17","author":[{"given":"Tong","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Thyroid and Head and Neck Surgery II, Jilin Provincial Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanshi","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Head and Neck Surgery I, 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