Background: Faulty apoptosis is a known mechanism that leads to resistance to radiotherapy. The application (WO2012016918A1) deals with a peptide useful for disrupting this resistance mechanism and enhancing the efficiency of radiotherapy.
Methods: A peptide consisting essentially of the N2 sequence of the RasGAP protein is conjugated to the HIV-TAT(48-57) cell permeation sequence. The DNA sequence encoding the peptide (TAT-RasGAP(317-326)) is synthesized and introduced into the host cells.
Results: TAT-RasGAP(317-326) is demonstrated to potentiate the efficacy of γ-irradiation-mediated cell killing both in tumor cell lines and in mouse tumor models, disregarding the status of p53, but not in non-cancer cells.
Conclusion: TAT-RasGAP(317-326) peptide favors apoptosis of tumor cells, but not normal cells in response to radiotherapy. The invention provides a specific method that is probably to be used in cancers that are radio-resistant.