E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling Article Swipe
Kazuhiko Yamada
,
Yusaku Hori
,
Satoshi Inoue
,
Yuji Yamamoto
,
Kentaro Iso
,
Hiroshi Kamiyama
,
Atsumi Yamaguchi
,
Takayuki Kimura
,
Mai Uesugi
,
Jun‐ichi Ito
,
Masahiro Matsuki
,
Kazutaka Nakamoto
,
Hitoshi Harada
,
Naoki Yoneda
,
Atsushi Takemura
,
Ikuo Kushida
,
Naomi Wakayama
,
Kenji Kubara
,
Yu Kato
,
Taro Semba
,
Akira Yokoi
,
Masayuki Matsukura
,
Takenao Odagami
,
Masao Iwata
,
Akihiko Tsuruoka
,
Toshimitsu Uenaka
,
Junji Matsui
,
Tomohiro Matsushima
,
K. Nomoto
,
Hiroyuki Kouji
,
Takashi Owa
,
Yasuhiro Funahashi
,
Yoichi Ozawa
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1158/0008-5472.can-20-0782
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1158/0008-5472.can-20-0782
The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the development of multiple types of cancer, and its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-catenin signaling pathway, disrupts the Wnt/β-catenin signaling pathway in HEK293 and adenomatous polyposis coli (APC)-mutated human gastric cancer ECC10 cells. It also inhibited tumor growth in an ECC10 xenograft model and suppressed polyp formation in the intestinal tract of ApcMin/+ mice, in which mutation of Apc activates the Wnt/β-catenin signaling pathway. E7386 demonstrated antitumor activity against mouse mammary tumors developed in mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice. Gene expression profiling using RNA sequencing data of MMTV-Wnt1 tumor tissue from mice treated with E7386 showed that E7386 downregulated genes in the hypoxia signaling pathway and immune responses related to the CCL2, and IHC analysis showed that E7386 induced infiltration of CD8+ cells into tumor tissues. Furthermore, E7386 showed synergistic antitumor activity against MMTV-Wnt1 tumor in combination with anti-PD-1 antibody. In conclusion, E7386 demonstrates clear antitumor activity via modulation of the Wnt/β-catenin signaling pathway and alteration of the tumor and immune microenvironments, and its antitumor activity can be enhanced in combination with anti-PD-1 antibody. Significance: These findings demonstrate that the novel anticancer agent, E7386, modulates Wnt/β-catenin signaling, altering the tumor immune microenvironment and exhibiting synergistic antitumor activity in combination with anti-PD-1 antibody.
Related Topics
Concepts
Wnt signaling pathway
Cancer research
Beta-catenin
Signal transduction
Tumor microenvironment
Mammary tumor
Adenomatous polyposis coli
Biology
Catenin
Cancer
Cell biology
Colorectal cancer
Breast cancer
Tumor cells
Genetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1158/0008-5472.can-20-0782
- https://cancerres.aacrjournals.org/content/canres/81/4/1052.full.pdf
- OA Status
- bronze
- Cited By
- 54
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3119280949
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3119280949Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1158/0008-5472.can-20-0782Digital Object Identifier
- Title
-
E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt SignalingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-01-06Full publication date if available
- Authors
-
Kazuhiko Yamada, Yusaku Hori, Satoshi Inoue, Yuji Yamamoto, Kentaro Iso, Hiroshi Kamiyama, Atsumi Yamaguchi, Takayuki Kimura, Mai Uesugi, Jun‐ichi Ito, Masahiro Matsuki, Kazutaka Nakamoto, Hitoshi Harada, Naoki Yoneda, Atsushi Takemura, Ikuo Kushida, Naomi Wakayama, Kenji Kubara, Yu Kato, Taro Semba, Akira Yokoi, Masayuki Matsukura, Takenao Odagami, Masao Iwata, Akihiko Tsuruoka, Toshimitsu Uenaka, Junji Matsui, Tomohiro Matsushima, K. Nomoto, Hiroyuki Kouji, Takashi Owa, Yasuhiro Funahashi, Yoichi OzawaList of authors in order
- Landing page
-
https://doi.org/10.1158/0008-5472.can-20-0782Publisher landing page
- PDF URL
-
https://cancerres.aacrjournals.org/content/canres/81/4/1052.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://cancerres.aacrjournals.org/content/canres/81/4/1052.full.pdfDirect OA link when available
- Concepts
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Wnt signaling pathway, Cancer research, Beta-catenin, Signal transduction, Tumor microenvironment, Mammary tumor, Adenomatous polyposis coli, Biology, Catenin, Cancer, Cell biology, Colorectal cancer, Breast cancer, Tumor cells, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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54Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 15, 2024: 11, 2023: 12, 2022: 11, 2021: 5Per-year citation counts (last 5 years)
- References (count)
-
55Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| publication_date | 2021-01-06 |
| publication_year | 2021 |
| referenced_works | https://openalex.org/W2006419043, https://openalex.org/W2621361823, https://openalex.org/W2520632143, https://openalex.org/W1971085650, https://openalex.org/W6741341122, https://openalex.org/W2419193153, https://openalex.org/W2262414037, https://openalex.org/W2291207840, https://openalex.org/W2116318030, https://openalex.org/W2442495408, https://openalex.org/W2580748679, https://openalex.org/W2890917067, https://openalex.org/W2954220199, https://openalex.org/W1498931318, https://openalex.org/W2952311394, https://openalex.org/W1994029539, https://openalex.org/W2069750786, https://openalex.org/W2760010857, https://openalex.org/W2771031544, https://openalex.org/W2914135414, https://openalex.org/W1994928797, https://openalex.org/W2948146865, https://openalex.org/W2811064737, https://openalex.org/W2115001053, https://openalex.org/W2053666128, https://openalex.org/W2034498760, https://openalex.org/W2131271579, https://openalex.org/W2169456326, https://openalex.org/W6684826817, https://openalex.org/W2100305481, https://openalex.org/W2179438025, https://openalex.org/W57306529, https://openalex.org/W2110160785, https://openalex.org/W2100463963, https://openalex.org/W2038122249, https://openalex.org/W2513473844, https://openalex.org/W1985987855, https://openalex.org/W2094464106, https://openalex.org/W2071937290, https://openalex.org/W2089399170, https://openalex.org/W1983710466, https://openalex.org/W1554815317, https://openalex.org/W4321429547, https://openalex.org/W6674752845, https://openalex.org/W2033618020, https://openalex.org/W2132686947, https://openalex.org/W2072420502, https://openalex.org/W2883209651, https://openalex.org/W2884371797, https://openalex.org/W2979927617, https://openalex.org/W2060070314, https://openalex.org/W6665569923, https://openalex.org/W2914345456, https://openalex.org/W2099069920, https://openalex.org/W2739392386 |
| referenced_works_count | 55 |
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| abstract_inverted_index.It | 73 |
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| abstract_inverted_index.be | 209 |
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| abstract_inverted_index.Apc | 98 |
| abstract_inverted_index.IHC | 155 |
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| abstract_inverted_index.mice | 133 |
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| abstract_inverted_index.ECC10 | 71, 80 |
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| abstract_inverted_index.genes | 141 |
| abstract_inverted_index.human | 68 |
| abstract_inverted_index.mice, | 93 |
| abstract_inverted_index.mice. | 120 |
| abstract_inverted_index.model | 82 |
| abstract_inverted_index.mouse | 109, 114 |
| abstract_inverted_index.novel | 222 |
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| abstract_inverted_index.polyp | 85 |
| abstract_inverted_index.roles | 7 |
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| abstract_inverted_index.types | 16 |
| abstract_inverted_index.using | 124 |
| abstract_inverted_index.virus | 117 |
| abstract_inverted_index.which | 48, 95 |
| abstract_inverted_index.E7386, | 33, 225 |
| abstract_inverted_index.HEK293 | 62 |
| abstract_inverted_index.active | 36 |
| abstract_inverted_index.agent, | 224 |
| abstract_inverted_index.cancer | 24, 70 |
| abstract_inverted_index.cells. | 72 |
| abstract_inverted_index.escape | 27 |
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| abstract_inverted_index.orally | 35 |
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| abstract_inverted_index.hypoxia | 144 |
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| abstract_inverted_index.analysis | 156 |
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| abstract_inverted_index.selective | 37 |
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| abstract_inverted_index.xenograft | 81 |
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| abstract_inverted_index.conclusion, | 183 |
| abstract_inverted_index.demonstrate | 219 |
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| abstract_inverted_index.infiltration | 161 |
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