Therapeutic Peptides in Cancer
Cancer is one of the leading causes of death globally with more than 100 different cancer types reported, owing to a vast genetic heterogeneity in cancer states. As conventional treatments present with challenges such as recurrences and resistance, newer alternatives such as peptide therapeutics and immunotherapy are being explored to provide advances towards better clinical outcomes.
Peptides used in cancer research broadly fit under the following categories:
- Cancer antigen
- Cancer-associated Pathway interfering peptides
- Drug delivery peptides
Cancer Antigens (Tumor antigens, Neoantigens)
Tumor derived, tumor associated antigens (TAA) or homing peptides are used as targets for the development of cancer vaccines (such as NY-ESO-1 peptide vaccine) as they illicit an immune response against cells containing the cancer antigen. Owing to differential expression in various tissues, some of these peptides serve as biomarkers and can also play immuno-modulatory roles within the immune landscape of cancer pathways such as Mucin, Melan-A-MART, PD-L1 etc.
More recently, tumor specific antigens or tumor specific neoantigens (TSNA) that arise from tumor cell mutations are being identified in a large number of cancer patients. These neoantigens, which are peptides are processed and presented to the T cells in association with MHC molecules to elicit an immune response against the underlying cancer.
New effective anticancer therapeutics
Cancer-associated pathway interfering peptides found naturally have been synthetically produced for use in cancer models to induce cell death through apoptotic and non-apoptotic mechanisms. For example, Shepherdin fragment, blocks the interaction between molecular chaperone Hsp90 and survivin, a caspase activation inhibitor.
Cancer cells exhibit an elevated apoptotic threshold and peptides that are able to induce apoptosis in tumor cells are increasingly seen as promising candidates for the development of new effective anticancer therapeutics.
Synthetic peptides that can target the apoptotic signal transduction cascades and/or function as pro-apoptotic agents bearing pharmaceutical potential are being developed. Examples include, several different caspases, peptides of the BCl2 family of proteins, etc.
Cell permeable peptides (CPP) such as TAT, or antennapedia, conjugated to anti-cancer drugs are under evaluation for their ability to penetrate and deliver anti-tumor molecules into cancer cells. Drug examples include small molecules like doxorubicin and paclitaxel, or biomolecules including oligonucleotides, plasmid DNA, and siRNA.