Therapeutic advancements in oncology, including targeted small-molecule inhibitors and immunotherapies, have significantly improved patient survival. However, these therapies often produce substantial systemic side effects that reach well beyond the tumor microenvironment. Among these, treatment-induced neurotoxicities, such as Chemotherapy-Induced Cognitive Impairment (CICI, commonly known as chemobrain) and Chemotherapy-Induced Peripheral Neuropathy (CIPN), represent critical clinical challenges that severely compromise patient quality of life. Growing evidence implicates the neuro-immune-gut axis in the development and progression of these toxicities, where systemic neuroinflammation, microglial activation, blood-brain barrier (BBB) compromise, and gut-microbiota dysbiosis interact to drive neural damage. Understanding the translational pharmacology of agents that can modulate these pathways is essential for developing effective protective and therapeutic strategies.
This Research Topic brings together translational and preclinical research on targeted small-molecule therapeutics and advanced nanomedicines designed to modulate the neuro-immune-gut axis and alleviate treatment-induced neurotoxicities. Drawing on medicinal chemistry, neurobiology, and oncology, this collection highlights pharmacological approaches that protect neural integrity without compromising anti-tumor efficacy. We welcome submissions that explore molecular mechanisms of neurotoxicity, lead optimization of neuroprotective agents, and advanced drug delivery strategies.
We encourage contributors to submit original research, reviews, mini-reviews, and perspective articles on themes including, but not limited to, the following:
Discovery, design, and preclinical evaluation of targeted small molecules (including quinazoline derivatives, pyrimidine-based pharmacophores, and repurposed agents) that mitigate neurotoxicity. Pharmacological modulation of neuroinflammatory and apoptotic pathways, such as the NLRP3 inflammasome, JAK/STAT signaling, canonical Wnt signaling, and Akt/PKB pathways, in the context of cancer therapy. Mechanistic insights into the gut-brain-microbiota axis and its influence on chemotherapy-induced cognitive and behavioral alterations. Targeted nanomedicine and advanced drug delivery systems, including polymeric or chitosan nanoparticles and extracellular vesicles, optimized for crossing the blood-brain barrier or achieving nose-to-brain delivery. Computational and in silico profiling, such as molecular dynamics simulations and molecular docking, to characterize small-molecule interactions with neuroprotective, immunomodulatory, or tumor-associated macrophage targets. Natural-product-derived compounds (such as fisetin, quercetin, morin, or safranal) and their synthesized derivatives as protective agents against chemotoxicity and neurodegeneration. Pharmacokinetic and pharmacodynamic modeling of neuroprotective agents in tumor-bearing models to ensure non-interference with anti-cancer efficacy.
Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Case Report
Clinical Trial
Data Report
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Methods
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
