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Development of novel diagnostic and therapeutic methods focusing on tumor microenvironmental factors

Therapeutic resistance is the major cause for a poor prognosis of cancer patients. Various cellular changes involved in the development of drug resistance in cancer cells were reported, besides, microenvironmental constituents, especially CAFs and extracellular matrix (ECM), can also be key regulators of the sensitivity to cancer cell-targeted therapy1. A crucial challenge is to understand how CAFs and ECM affect drug sensitivity. In our lab, by using human samples, we develop novel diagnostic and therapeutic methods focusing on tumor microenvironmental factors given by CAFs and ECM.

Development of novel diagnostic and therapeutic methods focusing on tumor microenvironmental factors

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  1. Ishii G, Ochiai A, Neri S. Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Advanced Drug Delivery Review 99(Pt B):186-962, 2016
  2. Yoshida T, Ishii G, Goto K, Neri S, Hashimoto H, Yoh K, Niho S, Umemura S, Matsumoto S, Ohmatsu H, Iida S, Niimi A, Nagai K, Ohe Y, Ochiai A. Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation. Clin. Cancer Res. 21(3):642-51, 2015
  3. Koriyama H, Ishii G, Yoh K, Neri S, Morise M, Umemura S, Matsumoto S, Niho S, Ohmatsu H, Tsuboi M, Goto K, Ochiai A. Presence of podoplanin-positive cancer-associated fibroblasts in surgically-resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy. J Cancer Res Clin Oncol. 141(7):1163-70, 2015
  4. Ishibashi M, Neri S, Hashimoto H, Miyashita T, Yoshida T, Nakamura Y, Udagawa H, Kirita K, Matsumoto S, Umemura S, Yoh K, Niho S, Tsuboi M, Masutomi K, Goto K, Ochiai A, Ishii G. CD200-positive cancer associated fibroblasts augment the sensitivity of Epidermal Growth Factor Receptor mutation-positive lung adenocarcinomas to EGFR Tyrosine kinase inhibitors. Sci Rep. 21;7:46662, 2017