3D layered co-culture model enhances Trastuzumab Deruxtecan sensitivity and reveals the combined effect with G007-LK in HER2-positive non-small cell lung cancer.

Autor: Shiraishi A; Div of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa-shi, Chiba, 277-8561, Japan., Oh-Hara T; Div of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan., Takahashi Y; Technical Research Institute, TOPPAN Holdings Inc., Japan; Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan., Uchibori K; Div of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Nishio M; Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan., Katayama R; Div of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa-shi, Chiba, 277-8561, Japan. Electronic address: ryohei.katayama@jfcr.or.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Sep 17; Vol. 725, pp. 150255. Date of Electronic Publication: 2024 Jun 11.
DOI: 10.1016/j.bbrc.2024.150255
Abstrakt: Human epidermal growth factor receptor 2 (HER2) aberrations are observed in various cancers. In non-small cell lung cancer, genetic alterations activating HER2, mostly exon 20 insertion mutations, occur in approximately 2-4% of cases. Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody-drug conjugate has been approved as the first HER2-targeted drug for HER2-mutant lung cancer. However, some cases are not responsive to T-DXd and the primary resistant mechanism remains unclear. In this study, we assessed sensitivity to T-DXd in JFCR-007, a patient-derived HER2-mutant lung cancer cell line. Although JFCR-007 was sensitive to HER2 tyrosine kinase inhibitors, it showed resistance to T-DXd in attachment or spheroid conditions. Accordingly, we established a three-dimensional (3D) layered co-culture model of JFCR-007, where it exhibited a lumen-like structure and became sensitive to T-DXd. In addition, an in-house inhibitor library screening revealed that G007-LK, a tankyrase inhibitor, was effective when combined with T-DXd. G007-LK increased the cytotoxicity of topoisomerase-I inhibitor, DXd, a payload of T-DXd and SN-38. This combined effect was also observed in H2170, an HER2-amplified lung cancer cell line. These results suggest that the proposed 3D co-culture system may help in evaluating the efficacy of T-DXd and may recapitulate the tumor microenvironment.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryohei Katayama reports financial support was provided by Japan Society for the Promotion of Science. Ryohei Katayama reports financial support was provided by Japan Agency for Medical Research and Development. Ryohei Katayama reports financial support was provided by the Nakatomi Foundation. Ryohei Katayama reports financial support was provided by Nippon Foundation. Ryohei Katayama reports financial support was provided by Takeda Science Foundation. Ryohei Katayama reports financial support was provided by Kobayashi Foundation for Cancer Research. Ken Uchibori reports financial support was provided by Japan Society for the Promotion of Science. Akari Shiraishi reports financial support was provided by Japan Science and Technology Agency. Ryohei Katayama reports a relationship with Chugai Pharmaceutical Co Ltd that includes: funding grants. Ryohei Katayama reports a relationship with Toppan Inc that includes: funding grants. Yuki Takahashi reports a relationship with Toppan Inc that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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