Influence of De Novo designed peptides on cancer development: a novel approach to skin cancer therapy

Malignant melanomas are resistant to conventional therapies such as chemotherapy, immunotherapy, radiation therapy and surgery. The patient's chances of survival often depend on melanoma’s early diagnosis and treatment; hence new effective therapeutic agents are required. Oncolytic virotherapy is a novel therapy that can be applied solely or in conjunction with the conventional therapies. In particular, some viruses such as myxoma virus (MV) have the ability to target and destroy cancer cells without harming the normal cells. Another type of a novel approach for cancer therapy is peptides which focus on small molecular weight of peptides.

Based on the properties of MV proteins, we used the bioactive peptide RRM-MV, designed by the Resonant Recognition Module (RRM), to assess the cytotoxicity and mode of action of the RRM-MV on skin cancer cells as an attempt to develop a targeted therapeutic peptide with high effectiveness. The non-bioactive peptides RRM-C and RRM-MV-C were also designed, using the RRM and were used a negative control peptides.

This study also outlines the characterization of molecular events in skin cancer cells that promote apoptosis pathway after peptide treatment as well as the influence of the bioactive peptide on Akt-activation.

The findings indicate the successful application of the RRM concept to design a bioactive peptide possessing strong tumoricidal activity with negligible toxicity on normal cells. This bioactive peptide could be developed as a potential cancer therapeutic. The RRM application to design bioactive peptides will open a new direction to the rational design of therapeutic agents for future cancer treatment.