American Association for Cancer Research
mct-23-0371_supplementary_figure_s11_suppsf11.pdf (96.66 kB)

Supplementary Figure S11 from Combination Therapy with EGFR Tyrosine Kinase Inhibitors and TEAD Inhibitor Increases Tumor Suppression Effects in EGFR Mutation–positive Lung Cancer

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posted on 2024-04-02, 07:21 authored by Tatsuya Ogimoto, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Masatoshi Yamazoe, Kentaro Hashimoto, Hiroshi Yoshida, Kazutaka Hosoya, Hitomi Ajimizu, Takashi Nomizo, Hironori Yoshida, Masatsugu Hamaji, Toshi Menju, Akihiko Yoshizawa, Hiroshi Date, Toyohiro Hirai

Supplementary Figure S11 shows immunofluorescent staining of H1975 cells treated with osimertinib.


Japan Society for the Promotion of Science (JSPS)

Japan Science and Technology Agency (JST)



EGFR-tyrosine kinase inhibitors (TKI) are the first-line therapies for EGFR mutation–positive lung cancer. EGFR-TKIs have favorable therapeutic effects. However, a large proportion of patients with EGFR mutation–positive lung cancer subsequently relapse. Some cancer cells survive the initial treatment with EGFR-TKIs, and this initial survival may be associated with subsequent recurrence. Therefore, we aimed to overcome the initial survival against EGFR-TKIs. We hypothesized that yes-associated protein 1 (YAP1) is involved in the initial survival against EGFR-TKIs, and we confirmed the combined effect of EGFR-TKIs and a YAP1–TEAD pathway inhibitor. The KTOR27 (EGFR kinase domain duplication) lung cancer cell lines established from a patient with EGFR mutation–positive lung cancer and commercially available PC-9 and HCC827 (EGFR exon 19 deletions) lung cancer cell lines were used. These cells were used to evaluate the in vitro and in vivo effects of VT104, a TEAD inhibitor. In addition, YAP1 involvement was investigated in pathologic specimens. YAP1 was activated by short-term EGFR-TKI treatment in EGFR mutation–positive lung cancer cells. In addition, inhibiting YAP1 function using siRNA increased the sensitivity to EGFR-TKIs. Combination therapy with VT104 and EGFR-TKIs showed better tumor-suppressive effects than EGFR-TKIs alone, in vitro and in vivo. Moreover, the combined effect of VT104 and EGFR-TKIs was observed regardless of the localization status of YAP1 before EGFR-TKI exposure. These results suggest that combination therapy with the TEAD inhibitor and EGFR-TKIs may improve the prognosis of patients with EGFR mutation–positive lung cancer.

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