Weimin Zuo, Siyuan Luo, Haixin Qin, Koon Ho Wong, Shirley W. I. Siu, Alexandre K. Tashima, Yehuda G. Assaraf, Hang Fai Kwok
Pancreatic cancer remains a highly lethal malignancy with limited therapeutic options, calling for innovative discovery of efficacious antitumor strategies. Here, we report on PCa2, an AI-derived anticancer lead peptide originating from the Candida albicans genome, which exhibits potent antitumor activity against pancreatic cancer both in vitro and in vivo. Mechanistic investigations suggest that PCa2 is associated with modulation of the ErbB–PI3K–AKT–mTOR–MYC signaling axis, accompanied by receptor internalization and lysosome-mediated degradation. Collectively, these findings identify PCa2 as a promising therapeutic lead candidate that modulates the ErbB–PI3K–AKT–mTOR-MYC axis and induces autophagy-associated cytotoxicity in pancreatic cancer.