Developmental Signaling Pathways at the Intersection of Brain Aging and Neuro-Oncology: Biomarkers, Microenvironment, and Translational Implications

Developmental signaling pathways, including Wnt, Notch, Hedgehog, PI3K/AKT/mTOR, TGF-β, and MAPK, serve as master regulators of neural specification, synaptic plasticity, and tissue homeostasis throughout life. Increasing evidence identifies these conserved molecular networks as a unifying biological framework linking neurodevelopment, brain aging, neurodegeneration, and neuro-oncology. Notably, many of the same signaling pathways that are hyperactivated in brain tumors to promote proliferation, invasion, and therapy resistance become dysregulated in Alzheimer’s, Parkinson’s, and Huntington’s diseases, often leading to opposing cellular outcomes: sustained growth and survival in cancer versus dysfunction, senescence, and cell death in neurodegeneration. The rapidly advancing field of cancer neuroscience has revealed complex bidirectional interactions among neurons, glia, immune cells, and the tumor microenvironment, demonstrating how tumors co-opt ancient developmental programs to drive progression and therapeutic resistance. Epigenetic regulation adds a critical layer that can rewire these networks in different contexts. This Research Topic will explore the shared and divergent mechanisms, convergent biomarkers, microenvironmental dynamics, and translational opportunities at this compelling intersection of developmental signaling, brain aging, and neuro-oncology.Despite growing evidence that developmental signaling pathways regulate neural development, brain aging, and tumorigenesis, these processes are still largely studied as separate biological phenomena. Consequently, the key mechanistic links among cellular plasticity, proliferation, senescence, neuroinflammation, and malignant transformation remain incompletely understood. A central unresolved question is why the same signaling networks that orchestrate neural plasticity and homeostasis during development later contribute to either malignant transformation or neurodegeneration and senescence – a “Janus-faced” behavior whose contextual determinants remain unclear. Another major challenge is explained how shared developmental and epigenetic programs can underlie both neurodegeneration and gliomagenesis despite their well-recognized inverse epidemiological association. Recent advances in single-cell and spatial multi-omics, epigenetic profiling, human iPSC-derived organoid and assembloid models, high-resolution neuroimaging, and functional genomics now offer unprecedented resolution to address these questions. This Research Topic aims to integrate discoveries across neurodevelopment, brain aging, and neuro-oncology – spanning adult malignancies such as glioblastoma and pediatric tumors such as medulloblastoma – to identify common biomarkers, microenvironmental mechanisms, signaling networks, and therapeutic vulnerabilities. By fostering multidisciplinary collaboration, we aim to accelerate translational strategies that improve diagnosis, prognosis, and targeted interventions for both age-related neurological disorders and brain cancers.This Research Topic welcomes contributions addressing the intersection of neurodevelopment, brain aging, and neuro-oncology. Areas of interest include, but are not limited to: (i) Molecular and cellular mechanisms involving Wnt, Notch, Hedgehog, PI3K/AKT/mTOR, TGF-β, MAPK, and related networks in neural development, cellular senescence, plasticity and brain tumor biology; (ii) Neural, immune, and tumor microenvironment interactions; including microglial and macrophage reprogramming across developmental, aging, and tumor-associated microenvironments; (iii) Biomarker discovery and validation for early detection, progression monitoring, and therapeutic stratification in neuro-oncological and neurodegenerative conditions; (iv) Epigenetic regulation, cellular senescence programs, and neuroinflammation as convergent or divergent processes; (v) Cancer neuroscience and neuron–tumor communication, including activity-dependent tumor growth and neuro-glial contributions to the tumor microenvironment; (vi) Neural stem and progenitor cell biology in homeostasis, aging, and tumorigenesis; (vii) Single-cell and spatial omics, computational systems biology; multi-omics integration, and advancing modeling approaches (organoids, assembloids, xenografts); (viii) Translational and therapeutic strategies targeting these pathways or their effectors for gliomas, medulloblastomas, brain metastases, and age-related neurological disorders. We invite original research articles, reviews, mini-reviews, perspective and methods articles. Contributions that integrate multi-omics or cross-disciplinary methodologies, bridge pediatric and adult populations or incorporate clinical or translational data are especially encouraged. This collection aims to catalyze new conceptual frameworks and collaborative advances to drive meaningful progress for patients facing these interrelated yet distinct disease spectra. Topic editors: Juliana Marisol Godínez-Rubí, Daniel Ortuño-Sahagún Source: https://www.frontiersin.org/research-topics/82526/developmental-signaling-pathways-at-the-intersection-of-brain-aging-and-neuro-oncology-biomarkers-microenvironment-and-translational-implications