Development of anti-cancer drug effect enhancers by transforming cancer-associated fibroblasts

DOI Web Site 28 References
  • IIDA Tadashi
    Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Department of Pathology, Nagoya University Graduate School of Medicine
  • MIZUTANI Yasuyuki
    Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine Department of Pathology, Nagoya University Graduate School of Medicine
  • YAMAO Kentaro
    Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
  • ISHIKAWA Takuya
    Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
  • ONO Eizaburo
    Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine
  • FUJISHIRO Mitsuhiro
    Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo
  • ENOMOTO Atsushi
    Department of Pathology, Nagoya University Graduate School of Medicine
  • KAWASHIMA Hiroki
    Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine

Bibliographic Information

Other Title
  • 癌関連線維芽細胞の形質改変による抗癌剤効果増強剤の開発

Abstract

<p>One characteristic of pancreatic cancer, considered incurable, is fibrosis in the interstitium and associated tissue sclerosis. Tissue stiffness is known to induce increased intrastromal pressure and vascular collapse, inhibiting the penetration of anticancer drugs into the interstitium with delivery to cancer cells. Cancer-associated fibroblasts (CAFs) play a central role in the development of fibrosis in the stroma. Various therapies targeting CAFs have been developed but have not yet been successful. In this study, we demonstrated that inducing the expression of Meflin, a marker and functional molecule of tumor suppressive CAFs, in CAFs improves the sensitivity to chemotherapy of pancreatic cancer. Furthermore, a compound library screening revealed that AM80, a synthetic retinoid, effectively induces the expression of Meflin in CAFs and improves sensitivity to chemotherapy with improved drug delivery. Based on these results, the authors are conducting a clinical trial of AM80 in combination with conventional anticancer agents to treat patients with unresectable pancreatic cancer to evaluate the efficacy of AM80.</p>

Journal

  • Suizo

    Suizo 38 (1), 37-43, 2023-02-28

    Japan Pancreas Society

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