Several potential molecular-targeted anticancer drugs focus on the inhibition of
receptor tyrosine kinase and tumour growth, but these
tyrosine kinase inhibitors (TKI) have been reported that the mutations of
kinase-related signal molecule genes in
cancer cells lead to the drug resistance. To overcome this issue, we have designed a novel targeting anticancer 'hybrid-
peptide'
EGFR-lytic peptide, in which
epidermal growth factor receptor (EGFR) binding
peptide is conjugated with a newly designed lytic-type
peptide containing cationic-rich
amino acids that disintegrates the cell membrane to kill
cancer cells. In this report, cytotoxic activity of
EGFR-lytic peptide was investigated in various human
cancer and normal cell lines. It was found that the resulting conformational change in the novel lytic
peptide enabled it to bind selectively to the membrane of
cancer cells, and due to its acquired synergistic action, hybrid
peptide demonstrated selective destruction of
cancer cells as swiftly as 10 min after exposure. Treatment with
EGFR-lytic peptide exerted a sufficient in vitro cytotoxic activity against TKI-resistant
cancer cells with K-ras mutations. Moreover, in vivo analyses revealed that this
peptide displayed significant antitumour activity in mouse xenograft models of both human K-ras mutation negative and positive
cancers. Thus, hybrid
peptide can be a unique and powerful tool for a new
cancer-targeted
therapy.