P18

P18 is a novel anticancer peptide, derived from the protein Arhgdia, investigated primarily for the treatment of breast cancer metastasis, but also active against pancreatic ductal adenocarcinoma and osteosarcoma cells. It is an α-helical peptide of approximately 1245 Da predicted to penetrate cell membranes by passive diffusion. P18 inhibits the viability, migration, and invasion of cancer cells, with minimal effects on non-tumor cells such as MSCs. Mechanistically, P18 suppresses the activity of small GTPases, specifically RhoA and Cdc42, which are implicated in cancer cell motility and metastasis, but does not reduce their expression. It promotes apoptosis via upregulation of c-Cas 3 and downregulation of proto-oncoproteins. A modified form, Ac-P18-NH2 (N-terminal acetylation, C-terminal amidation), demonstrated enhanced anticancer activity. P18 also shows synergy with chemotherapeutic agents (cisplatin, taxol) by lowering their IC50 and has been shown to reduce osteoclast maturation, thereby mitigating bone loss from metastasis.