Peptide Therapeutics for Solid Tumors: Functional Classes, AI-Enhanced Discovery and Clinical Advances

Solid tumors, the most prevalent form of malignancy, pose therapeutic challenges distinct from hematologic malignancies due to their complex biology, including high tumor heterogeneity, a dense extracellular matrix (ECM), an immunosuppressive tumor microenvironment (TME), and multifaceted drug resistance. Peptide drugs have emerged as a focal point in precision oncology, combining the deep tissue penetration of small molecules with the high target specificity, low immunogenicity, and sequence designability of antibodies. This review systematically summarizes advancements in peptide-based therapeutics for solid tumors from 2020 to 2025. These agents are categorized by function into five classes: tumor-homing peptides, surface receptor antagonist/inhibitory peptides, interfering peptides, peptide vaccines, and cell-penetrating peptides as delivery tools. We also highlight the transformative role of artificial intelligence (AI) in peptide design and discovery. Finally, we discuss outcomes from clinical trials of peptide drugs in solid tumors, underscoring their potential as multifunctional agents in this setting.