From Mechanism to Medicine: Peptide-Based Approaches for Cancer Diagnosis and Therapy

Therapeutic peptides have rapidly evolved into multifunctional tools for precision oncology, offering molecular specificity and biocompatibility. Their roles in cancer therapy, however, are inherently overlapping. The same peptide can function as a targeting ligand, a cell-penetrating motif, a therapeutic effector, or a structural component of peptide-drug conjugates (PDCs), nanoparticle (NP) systems, and radionuclide constructs. This functional convergence makes rigid classification challenging. In this review, we therefore organize peptide modalities according to their dominant therapeutic function while acknowledging the fluid boundaries between categories. Firstly, we outline the main functional classes of therapeutic peptides, covering their use as targeting ligands and their roles as active agents (i.e., receptor agonists/antagonists, intracellular protein-protein interaction modulators, etc.). Additionally, we summarize their application in peptide-drug conjugates (PDCs), peptide-guided radionuclides, and cancer vaccines, integrating key mechanistic principles and clinical evidence. Finally, we discuss the major translational barriers to clinical use and how they might be overcome. The developments in peptide engineering position them as adaptable, multifunctional platforms capable of improving precision, reducing toxicity, and advancing personalized cancer care.