Targeting Tumor Dormancy and Recurrence: Molecular Mechanisms and Peptide Therapeutic Delivery

ABSTRACT Tumor dormancy is a clinically challenging but physiologically significant aspect of cancer development, characterized by disseminated tumor cells that persist in non‐proliferative, quiescent state and frequently serving as a risk factor of recurrence. Although extensive progress has been made in understanding cancer progression and metastasis, strategies for reliably detecting and eliminating dormant tumor cells remain limited. This review aims to evaluate the current understanding of the molecular mechanisms underlying tumor dormancy, cellular quiscence, angiogenic processes, immune surveillance, and the complex roles of the tumor microenvironment, including extracellular matrix remodeling, metabolic adaptation and niche protection in tumor dormancy. Particular attention is given to the challenges associated with detecting and eliminating dormant cells, because these cells exhibit resistance to conventional therapies and reveal evasion of immune responses. Furthermore, we highlight peptide‐based strategies as promising platforms for detection, modulation and elimination of dormant tumor cells. These include tumor‐penetrating peptides, peptide‐drug conjugates, self‐assembling peptide nanostructures, and hydrogel–based delivery systems designed to disrupt dormancy‐maintaining niches or sensitize dormant cells to therapeutic intervention. The review also provides a summary of recent preclinical and clinical developments in peptide‐based treatments and outlines approaches to overcome translational challenges in targeting tumor dormancy. By integrating advances in peptide engineering with the biological principles of tumor dormancy, this review underscores the potential of peptide‐based platforms to improve therapeutic outcomes and reduce cancer recurrence.