Therapeutic peptides for cancer therapy. Part II – cell cycle inhibitory peptides and apoptosis-inducing peptides

Abstract

Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

Increasing the range of drug targets

“…14 The competitive inhibitors are able to mask an interaction domain and make this domain inaccessible for the natural interaction partner which in turn is required for proper function and finally for the implementation of a particular cellular phenotype. 15,16 In a next step, these peptide ligand interactions with crucial domains of target proteins can be further exploited in high throughput screening systems to find low molecular weight compounds which act as functionally equivalent analogs.…”

Promises of Apoptosis-Inducing Peptides in Cancer Therapeutics

“…A major concern in therapeutic development is therefore drug delivery. For these reasons, effort has been put into developing efficient delivery strategies including nano-particle-, polycationic-and lipid-based methods [11]. However, only a few of them have reached clinical trials [9].…”

“…Finally, they can be produced easily and at low cost. All these advantages have made the anti-cancer peptide research field very active lately as reported in a number of interesting recent reviews [6][7][8][9][10][11][12].…”

Cell Cycle and Energy Metabolism in Tumor Cells: Strategies for Drug Therapy

“…The importance of these CDK inhibitor proteins can be appreciated by the observation that inactivation of INK4a is one of the most frequent genetic traits in tumorigenesis. Whilst therapy with peptides show great promise, there are technical problems pertaining to the delivery of these synthetic peptides, and so far most of the experiments conducted have been carried out with cell lines [22].…”