Peptide Drug Conjugates (PDCS): The Next Generation of Targeted Therapy

Peptide-Drug Conjugates (PDCs) represent the next technological step forward in targeted cancer therapy, building on the framework established by Antibody-Drug Conjugates.The aim of the research in this field is to develop highly selective and potent agents capable of delivering an ultra-toxic payload directly into malignant cells.This should maximize the therapeutic efficiency while at the same time minimizing systemic damage.This rationale for the research is underpinned by the inherent advantages of peptides, as their small molecular size, 2-20 kDa, allows superior tumour penetration and low immunogenicity, enabling cost-efficient and highly homogeneous synthesis.PDCs are modular systems made of a tumour-homing peptide, chemical linker, and cytotoxic payload.Most research is focused on the attempts of overcoming core limitations, such as a short half-life because of rapid renal clearance and metabolic instability of a peptide backbone.The results of clinical translation reflect these problems faced by this class of drug conjugates.Currently, only the radionuclide PDC Lutathera has retained FDA approval, whereas Pepaxto, melphalan flufenamide, has seen its approval withdrawn from the US market.Despite those regulatory and technical barriers, the conclusion remains optimistic.The field is rapidly moving with the implementation of advanced peptide modification technologies, like cyclization and PEGylation, and the strategic integration of Computational Software and Artificial Intelligence methods for rational de novo design and in silico screening, which accelerate the development of a new generation of stable and highly effective targeted treatments for cancer.