在世界范围内，胰腺癌 (PC) 是一个主要的健康问题，2020 年将有近 50 万人被诊断出患有 PC。在美国，到 2023 年将有超过 64,000 名成年人被诊断出患有 PC。PC 对当前可用的治疗方法具有高度抵抗力，并且标准护理化疗会导致严重的副作用。大多数 PC 患者对临床治疗有抵抗力。联合治疗显示出优于单药治疗的疗效。然而，由于治疗相关的毒性，大多数治疗未能显示出总生存率的显着改善。开发有效的临床有用的 PC 疗法仍然是一个挑战。在此，我们展示了一种创新途径调节剂 p53-Activator Wnt Inhibitor-2 (PAWI-2) 对人类胰腺癌干细胞（即 hPCSC、FGβ3 细胞）产生的肿瘤的功效。 PAWI-2 是一种有效的肿瘤生长抑制剂。在本研究中，我们表明 PAWI-2 能有效抑制雄性和雌性小鼠的异种移植模型中 hPCSC 肿瘤的生长。 PAWI-2 以无毒方式抑制肿瘤。与媒介物处理的动物相比，PAWI-2 调节肿瘤的分子调节剂。抗癌结果表明 PAWI-2 的体内功效可能与体外抑制 FGβ3 细胞的效力相关。 PAWI-2 代表了一种对抗 PC 的安全新方法。© 2024。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下公司）的独家许可。

Worldwide, pancreatic cancer (PC) is a major health problem and almost 0.5 million people were diagnosed with PC in 2020. In the United States, more than 64,000 adults will be diagnosed with PC in 2023. PC is highly resistant to currently available treatments and standard of care chemotherapies cause serious side effects. Most PC patients are resistant to clinical therapies. Combination therapy has showed superior efficacy over single-agent treatment. However, most therapy has failed to show a significant improvement in overall survival due to treatment-related toxicity. Developing efficacious clinically useful PC therapies remains a challenge. Herein, we show the efficacy of an innovative pathway modulator, p53-Activator Wnt Inhibitor-2 (PAWI-2) against tumors arising from human pancreatic cancer stem cells (i.e., hPCSCs, FGβ3 cells). PAWI-2 is a potent inhibitor of tumor growth. In the present study, we showed PAWI-2 potently inhibited growth of tumors from hPCSCs in orthopic xenograft models of both male and female mice. PAWI-2 worked in a non-toxic manner to inhibit tumors. Compared to vehicle-treated animals, PAWI-2 modulated molecular regulators of tumors. Anti-cancer results showed PAWI-2 in vivo efficacy could be correlated to in vitro potency to inhibit FGβ3 cells. PAWI-2 represents a safe, new approach to combat PC.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.