Editorial: Peptides as cancer therapeutics

Abstract

Of the over one hundred anticancer drugs approved for patient use in the United States, the majority are small molecule cytotoxic drugs. Some are proteins such as interferon, interleukin-2, and monoclonal antibodies; only a handful are peptides. Gonadotropin releasing hormone analogue is an example of an anti-cancer peptide that has been used successfully as first line therapy for metastatic hormonal responsive prostate cancer, and it causes few side effects. It works by suppressing testosterone production which in turn inhibits prostate cancer growth. However, with few exceptions, most of the anticancer agents in use nowadays are rather non-specific and cause significant undesirable side effects on patients. There is accordingly a need for the development of new and effective cancer therapeutics. With the major advances in our basic understanding of oncogenesis and the amazing technologic development in recent years in genomics, proteomics, and drug discovery tools such as combinatorial chemistry, computational chemistry, and high throughput assays, there is genuine hope that more effective and less toxic anti-cancer drugs will be developed in the next decade or two. These drugs are likely to be target specific and less toxic. Although many of these drugs being developed are small molecules or proteins, several are peptides. This issue of Peptide Science highlights some of the recent developments in using peptides as cancer therapeutics. In the first article, Hamel describes the biochemical effects of a number of naturally occurring antimitotic peptides that target tubulin. These compounds are derived from plants, marine animals or microorganisms. They include phomopsins, ustiloxins, dolastatin, cemadotin, crytophysin, hemiasterlin, criamide, vitilevuamide, tubulysin, moroidin, and celogentin. Then, Froidevaux and Eberle outline the biochemistry of somatostatin and its five receptor subtypes. They summarize the literature on the use of unlabeled somatostatin analogues in the treatment of a number of different human cancers, and outline the development of radiolabeled somatostatin analogues as cancer targeting agents. This latter approach leads naturally into the subsequent paper by Lam and colleagues, where the rationale for the development of peptides-rather than monoclonal antibodies-as targeting agents is presented. The literature on using phage display or one-bead one-compound combinatorial peptide libraries to identify cell-surface targeting peptides is reviewed, and applications of these peptides to cancer targeting and cancer diagnostics are detailed. The final paper by Kaumaya and his colleagues surveys the literature on the use of peptides as cancer vaccines in patients. It also describes the ongoing research in the authors' laboratory relating to the use of co-stimulatory molecules and cytokines to augment immune responses. Peptides are likely to play a very important role in the treatment of cancer in the future, particularly in the areas of cell surface targeting and tumor peptide vaccines. As such, we hope readers will find this issue of Peptide Science both topical and stimulating.