| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-12-18 |
| タイトル |
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タイトル |
ATR inhibition activates cancer cell cGAS/STING-interferon signaling and promotes antitumor immunity in small-cell lung cancer |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Taniguchi, Hirokazu
Chakraborty, Subhamoy
Takahashi, Nobuyuki
Banerjee, Avisek
Caeser, Rebecca
Zhan, Yingqian A.
Tischfield, Sam E.
Chow, Andrew
Nguyen, Evelyn M.
Villalonga, Álvaro Quintanal
Manoj, Parvathy
Shah, Nisargbhai S.
Rosario, Samantha
Hayatt, Omar
Qu, Rui
de, Stanchina Elisa
Chan, Joseph
Mukae, Hiroshi
Thomas, Anish
Rudin, Charles M.
Sen, Triparna
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Patients with small-cell lung cancer (SCLC) have poor prognosis and typically experience only transient benefits from combined immune checkpoint blockade (ICB) and chemotherapy. Here, we show that inhibition of ataxia telangiectasia and rad3 related (ATR), the primary replication stress response activator, induces DNA damage–mediated micronuclei formation in SCLC models. ATR inhibition in SCLC activates the stimulator of interferon genes (STING)–mediated interferon signaling, recruits T cells, and augments the antitumor immune response of programmed death-ligand 1 (PD-L1) blockade in mouse models. We demonstrate that combined ATR and PD-L1 inhibition causes improved antitumor response than PD-L1 alone as the second-line treatment in SCLC. This study shows that targeting ATR up-regulates major histocompatibility class I expression in preclinical models and SCLC clinical samples collected from a first-in-class clinical trial of ATR inhibitor, berzosertib, with topotecan in patients with relapsed SCLC. Targeting ATR represents a transformative vulnerability of SCLC and is a complementary strategy to induce STING-interferon signaling–mediated immunogenicity in SCLC. |
|
言語 |
en |
| 書誌情報 |
en : Science Advances
巻 10,
号 39,
p. art. no. eado4618,
発行日 2024-09-27
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| 出版者 |
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出版者 |
American Association for the Advancement of Science |
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言語 |
en |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
2375-2548 |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1126/sciadv.ado4618 |
| 権利 |
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権利情報 |
© 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). |
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言語 |
en |
| 著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 引用 |
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内容記述タイプ |
Other |
|
内容記述 |
Science Advances, 10 (39), art. no. eado4618; 2024 |
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言語 |
en |
SA10_eado4618.pdf (2.4 MB)
