Peptide-Based Therapeutics for Oncology

Abstract

The development of peptide-based drugs, which are usually synthetic analogues of endogenous peptides, is currently one of the most topical directions in drug development. Among them, antitumor peptide-based drugs are of great interest. Anticancer peptides can be classified into three main groups based on their mechanism of action: inhibitory, necrosis-inducing and pro-apoptotic peptides. As an antitumor therapy, peptides are considered to have at least the same efficacy as chemotherapy or surgical treatment, but offer advantages in terms of safety and tolerability, given that chemotherapy is usually characterized by severe adverse effects, and surgery carries additional risks for patients. Short peptides have a number of benefits over other molecules. First, compared with full-length proteins and antibodies, short peptides are less immunogenic, more stable ex-vivo (prolonged storage at room temperature), and have better tumor or organ permeability. Moreover, the production of such short peptide-based drugs is more cost effective. Second, in comparison with small organic molecules, peptides have higher efficacy and specificity. Finally, due to the fact that the main products of peptide metabolism are amino acids, these drugs are usually characterized by lower toxicity. Short peptides have a highly selective mechanism of action, thereby demonstrating low toxicity. Furthermore, with the addition of different stabilizing structural modifications, as well as novel drug delivery systems, the peptide-based drugs are proving to be promising therapeutics for cancer mono- or polytherapy. However, challenges remain including that endogenous and synthetic peptide molecules can be oncogenic. Therefore, it is important to investigate whether peptides contribute to tumor growth. In order to answer such questions, numerous preclinical and clinical studies of peptide-based therapeutics are currently being conducted.