Chemo-Sensing and Efflux: Targeting Ectopic Taste Receptors and Transporters at the Brain Barriers

The development of effective therapeutics for Central Nervous System (CNS) malignancies and neurological disorders faces two critical hurdles: identifying novel, specific molecular targets and overcoming the formidable selection mechanisms of the brain barriers.

Recent evidence suggests that “taste” receptors (TAS1R and TAS2R families) are not confined to the tongue but are expressed ectopically in various tissues, including cancer cells, the brain endothelium, and the choroid plexus. Beyond their chemosensory role, these receptors are emerging as modulators of neuronal signalling, glial activity, and CNS homeostasis. Their role in modulating metabolic reprogramming and drug resistance offers a new frontier in neuropharmacology. Concurrently, the Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB) function not just as physical walls, but as metabolic and transport barriers, heavily regulated by ATP-binding cassette (ABC) transporters that actively pump chemotherapeutics and neurotherapeutics, out of the CNS.

The neuropharmacological implications of this interplay are far-reaching: from glioma resistance to temozolomide, to the potential role of ectopic taste receptors in modulating neuroinflammation and the CNS response to xenobiotics.

This Research Topic aims to bridge these fields by exploring the pharmacological interplay between ectopic sensory receptors, barrier integrity, and drug transport mechanisms. We invite researchers to submit Original Research, Reviews, and Methods papers that investigate the molecular mechanisms governing drug transport and target engagement in neurological and CNS oncological contexts.

Topics covered include, but are not limited to:

1. Neuropharmacology of Brain Barriers (“Transporters and Barrier Metabolism”)

The regulation of ABC transporters (e.g., P-gp, BCRP/ABCG2, MRPs) at the BBB and BCSFB in the context of CNS drug pharmacokinetics and therapeutic failure.

Impact of metabolic enzymes (e.g., CYP450s) at the neurovascular unit on drug bioavailability and neurotoxicity.

Strategies to modulate transporter activity to enhance CNS penetration of chemotherapeutics and neurotherapeutics.

The role of brain barriers in shaping drug exposure in both neuro-oncological and non-oncological CNS conditions.

2. Ectopic Taste Receptors as CNS Pharmacological Targets

Characterizing the expression and function of bitter (TAS2R) and sweet (TAS1R) receptors in non-gustatory tissues, specifically in gliomas, neurons, glial cells, and barrier epithelia.

Investigating downstream signaling of these receptors and their potential to reverse chemoresistance or alter drug metabolism and neuronal excitability.

The potential of taste receptors to regulate barrier permeability or tight junction proteins and their impact on CNS drug access.

The role of ectopic taste receptors in neuroinflammatory signaling and their potential as therapeutic targets in CNS diseases beyond oncology.

3. Pharmacokinetics and Drug Delivery to the CNS

Novel formulations (nanoparticles, liposomes) designed to bypass ABC efflux pumps for both anti-tumor and neuroactive drug delivery.

Pharmacokinetic modelling of drug distribution across CNS barriers with focus on brain exposure and target engagement.

Correlating receptor expression profiles with drug response and transport efficiency in CNS tumors and neurological disease models.

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
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• ... View all formats

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:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: ABC Transporters, Blood-Brain Barrier (BBB), Blood-CSF Barrier, Ectopic Taste Receptors (TAS2R), CNS Drug Delivery, Chemoresistance, Neuropharmacology, Neuroinflammation, Glioma, Neurovascular Unit, CNS Drug Penetration

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.