Effect of PAWI-2 on pancreatic cancer stem cell tumors

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 caus...

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Bibliographic Details
Published in:Investigational new drugs 2024-08, Vol.42 (4), p.353-360
Main Authors: Cashman, John R., Cashman, Emily A.
Format: Article
Language:English
Subjects:
Animal models
Biocompatibility
Cancer therapies
Effectiveness
Inhibitors
Medicine
Medicine & Public Health
Oncology
Pancreatic cancer
Pharmacology/Toxicology
Side effects
Stem cells
Toxicity
Tumors
Wnt protein
Xenotransplantation
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Summary: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, FGβ 3 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 FGβ 3 cells. PAWI-2 represents a safe, new approach to combat PC.
ISSN:0167-6997
1573-0646
1573-0646
DOI:10.1007/s10637-024-01447-x