Sequential Activation of Senescence and Apoptosis by ONG41008 Eliminated the Human Pancreatic Ductile Adenocarcinoma in nude mice and xenografted human lung cancer

Abstract

Current therapeutic limitations associated with pancreatic ductal adenocarcinoma (PDAC) are still evident. We have found that ONG41008, the first human synthetic polyphenol, is able to eradicate PDAC in a nude mouse model. ONG41008 is known to potently attenuate human TGF-{beta} production, inducing both anti-fibrotic capacity and anticancer potential through senescence-coupled apoptosis (SCA). These interesting observations closely paralleled ONG41008s ability to inhibit PDACs, and as expected, ONG41008 alone was able to actually ablate engrafted PDACs in nude mice. Interestingly, the anti-PD 1 developed by MSD did not appear to act on immune activation of exhausted Cd8+ T cells in the tumor microenvironment (TME), but primarily on engrafted PDAC blood vessels. These observations support the latest report from MSD. A549 cells known to be a well appreciated human lung adenocarcinoma cell line were treated with ONG41008. Consistent with the prior observations ONG41008 notably induced SCA. and when A549 cells were xenografted into mice daunting tumor formations were noticed. Upon stimulation with ONG41008 via direct intramural injection of these tumors tumor volumes were rapidly regressed. Taken together, we believe that ONG41008 could be a multifaceted anti-cancer agent not only against PDAC but also against other aggressive cancers such as lung cancer.