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Therapeutic Peptides for Treating Cancer

Peptides, either natural or synthetic, have seen increased application as therapeutic agents in recent years. In 2012, in addition to almost 80 peptides on the market, approximately 200 more have been reported to be in clinical phases and 400 are in advanced preclinical stages. Recently, peptide drugs targeting disorders of metabolic pathways or cancer are also demonstrat­ing potential applications in other clinical fields, such as cardiovascular, CNS, gastrointestinal and autoimmune diseases. This development marks a noticeable trend because towards the end of the previous century the use of peptides for the treatment of diseases was very lim­ited. The hope is that the development of new improved peptide based therapeutics may change this in the future.

The three therapeutic peptides goserelin, leuprolide and octreotide are already used to treat cancer, either directly or in the treatment of episodes associated with cancer tumors.

Goserelin acetate, the salt of a decapeptide, is an injectable gonadotropin releasing hormone superagonist, also known as a luteinizing hormone releasing hormone agonist. A superagonist is a compound that can bind to a receptor and activate it more strongly than the naturally produced activating molecule. Goserelin is used to suppress production of the sex hormones in the treatment of breast and prostate cancer and to treat hormone-sensitive cancers of the breast and prostate.

Leuprolide acetate is a gonadotropin-releasing hormone or luteinizing-hormone-releasing hormone analog used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions, precocious puberty, and to control ovarian stimulation in In-Vitro Fertilization.

Octreotide, a octapeptide, is a somatostatin mimic.  The peptide hormone somatostatin regulates the endocrine system, affects neurotransmission and cell proliferation via interaction with G protein-coupled somatostatin receptors and inhibits the release of numerous secondary hormones. Octreotide is also a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. The salt form of the peptide, octreotide acetate, is approved by the Food and Drug Administration (FDA) to be used as an injectable depot formulation for the treatment of growth hormone producing tumors, pituitary tumors that secrete thyroid stimulating hormone, diarrhea and flushing episodes associated with carcinoid syndrome, and diarrhea in patients with vasoactive intestinal peptide-secreting tumors.

In addition, host defense peptides are known to be present in most living species. These peptides exhibit a diverse range of functions in­cluding the direct killing of pathogens, immune-modulating properties and some host defense peptides have been reported to be potent against cancer cells and animal models have shown that several host defense peptides can confer complete and permanent tumor regression of different types of solid tumors.
Peptides that inhibit or modulate cell signaling interactions needed for cancer growth may also be used as anticancer agents. These types of therapeutic peptides have great potential as anti-cancer agents because they can be rationally designed to increase their target specificity and the following types have been reported so far: receptor-interacting compounds, inhibitors of protein-protein interaction, enzymes inhibitors; nucleic acid-interacting compounds, as well as active peptides for which no mechanism of action has been found yet.

Natural bioactive peptides derived from different foods represent another source of health-enhancing or cancer fighting compounds. Different studies indicate that it is possible that many of these peptides may be released during digestion in the human stomach or during food processing from various plant and animal proteins, especially milk, soy, and fish proteins. In addition, a number of studies focusing on marine bioactive peptides have identified many peptides and depsipeptides with anticancer potential. These types of peptides been extracted from various marine animals like tunicates, sponges, soft corals, sea hares, nudibranchs, bryozoans, sea slugs, and other marine organisms.

Drug design approaches that capitalize on structure-activity relationships found in natural inhibitory peptides are powerful tools for the discovery of novel, stable peptide mimics that exhibits unique high-affinity binding to human protein or peptide receptor targets for the development of future anticancer peptide therapeutics.

Peptides used as therapeutic agents for the treatment of cancer have gained momentum in recent years. The activity of different peptides that can be used for this type of treatment is attributed to mechanisms that restrict tumor growth. These can include the inhibition of angiogenesis, protein-protein interactions, enzymes, proteins, signal transduction pathways, or gene expression, or anticancer peptides that act as specific receptor antagonist. In addition, some peptides may also mediate the induction of apoptosis, the programmed cell death, in tumors.


References:

Albericio & Kruger;Therapeutic peptides.  Future Med. Chem. (2012) 4(12), 1527-1531.
Diana Gaspar, A. Salomé Veiga and Miguel A. R. B. Castanho < 
http://www.frontiersin.org/Community/WhosWhoActivity.aspx?sname=MiguelCastanho&UID=52339 > ; From antimicrobial to anticancer peptides. A review.

Front. Microbiol., 01 October 2013 | doi: 10.3389/fmicb.2013.00294.

Thundimadathil J.; Cancer treatment using peptides: current therapies and future prospects. J Amino Acids. < 
http://www.ncbi.nlm.nih.gov/pubmed/23316341 > 2012;2012:967347. doi: 10.1155/2012/967347. Epub 2012 Dec 20.

Guadalupe-Miroslava Suarez-Jimenez, Armando Burgos-Hernandez and Josafat-Marina Ezquerra-Brauer; Bioactive Peptides and Depsipeptides with Anticancer Potential: Sources from Marine Animals. Mar. Drugs 2012, 10, 963-986; doi:10.3390/md10050963.