Abstract

TASK-3 potassium channels have emerged as important regulators in several aspects of cancer pathophysiology. Overexpression of TASK-3 occurs in a broad spectrum of cancers, including breast, lung, ovarian, colorectal cancers, and melanoma. Genetic or pharmacological inhibition of TASK-3 has been shown to suppress tumorigenic properties. Despite the strong evidence, the development of selective TASK-3 inhibitors remains limited. In this review, we analyze the current evidence supporting TASK-3 as an oncogenic target, with emphasis on peptide-based inhibitors and advanced delivery strategies. Also, we review the landscape of TASK-3 modulation across different cancer types, summarize known mechanisms of ion channel inhibition, and highlight the advantages of peptides for achieving target selectivity and specificity. We further explore nanoconjugate delivery systems to improve peptide stability, bioavailability, and tumor targeting. Finally, we outline rational design methods, phage display technologies, and electrophysiological validation as an integrated pipeline for developing next-generation TASK-3 inhibitors. Together, these approaches delineate a strategic and technical framework for advancing selective TASK-3-targeted therapeutics in oncology.