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Citations to this article

Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus
Warren Floyd, … , Diana M. Cardona, David G. Kirsch
Warren Floyd, … , Diana M. Cardona, David G. Kirsch
Published May 18, 2023
Citation Information: J Clin Invest. 2023;133(13):e149310. https://doi.org/10.1172/JCI149310.
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Research Article Oncology Article has an altmetric score of 17

Atrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus

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Abstract

ATRX is one of the most frequently altered genes in solid tumors, and mutation is especially frequent in soft tissue sarcomas. However, the role of ATRX in tumor development and response to cancer therapies remains poorly understood. Here, we developed a primary mouse model of soft tissue sarcoma and showed that Atrx-deleted tumors were more sensitive to radiation therapy and to oncolytic herpesvirus. In the absence of Atrx, irradiated sarcomas had increased persistent DNA damage, telomere dysfunction, and mitotic catastrophe. Our work also showed that Atrx deletion resulted in downregulation of the CGAS/STING signaling pathway at multiple points in the pathway and was not driven by mutations or transcriptional downregulation of the CGAS/STING pathway components. We found that both human and mouse models of Atrx-deleted sarcoma had a reduced adaptive immune response, markedly impaired CGAS/STING signaling, and increased sensitivity to TVEC, an oncolytic herpesvirus that is currently FDA approved for the treatment of aggressive melanomas. Translation of these results to patients with ATRX-mutant cancers could enable genomically guided cancer therapy approaches to improve patient outcomes.

Authors

Warren Floyd, Matthew Pierpoint, Chang Su, Rutulkumar Patel, Lixia Luo, Katherine Deland, Amy J. Wisdom, Daniel Zhu, Yan Ma, Suzanne Bartholf DeWitt, Nerissa T. Williams, Alexander L. Lazarides, Jason A. Somarelli, David L. Corcoran, William C. Eward, Diana M. Cardona, David G. Kirsch

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Total citations by year

Year: 2025 2024 2023 2009 Total
Citations: 2 7 2 1 12
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (12)

Title and authors Publication Year
Novel intravenous formulation for radiosensitization in osteosarcoma treatment
Zeng H, Feng H, Zhang C, Kang Z, Wu J, Zhao X, Huang A, Xu Y, Huang Y, Xu H, Gong M
Materials Today Bio 2025
Loss of function of Atrx recapitulates phenotypes of alternative lengthening of telomeres in a primary mouse model of sarcoma
Pierpoint M, Floyd W, Wisdom AJ, Luo L, Ma Y, Dickson BC, Waitkus MS, Kirsch DG
iScience 2025
Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas
Hariharan S, Whitfield BT, Pirozzi CJ, Waitkus MS, Brown MC, Bowie ML, Irvin DM, Roso K, Fuller R, Hostettler J, Dharmaiah S, Gibson EA, Briley A, Mangoli A, Fraley C, Shobande M, Stevenson K, Zhang G, Malgulwar PB, Roberts H, Roskoski M, Spasojevic I, Keir ST, He Y, Castro MG, Huse JT, Ashley DM
Nature Communications 2024
Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies
Zhang J, Yu S, Peng Q, Wang P, Fang L
Cancer biology & medicine 2024
The Future of Targeted Therapy for Leiomyosarcoma.
Denu RA, Dann AM, Keung EZ, Nakazawa MS, Nassif Haddad EF
Cancers 2024
STING is significantly increased in high-grade glioma with high risk of recurrence
Zhong M, Long M, Han C, Ji S, Yang Q
OncoImmunology 2024
ATRX and Its Prognostic Significance in Soft Tissue Sarcoma.
Cullen MM, Floyd W, Dow B, Schleupner B, Brigman BE, Visgauss JD, Cardona DM, Somarelli JA, Eward WC
Sarcoma 2024
ATRX guards against aberrant differentiation in mesenchymal progenitor cells
Fang Y, Barrows D, Dabas Y, Carroll TS, Singer S, Tap WD, Nacev BA
Nucleic Acids Research 2024
Telomeres and telomerase in Sarcoma disease and therapy.
Huang J, Feng Y, Shi Y, Shao W, Li G, Chen G, Li Y, Yang Z, Yao Z
International journal of medical sciences 2024
Loss of function of Atrx leads to activation of alternative lengthening of telomeres in a primary mouse model of sarcoma
Pierpoint M, Floyd W, Wisdom AJ, Luo L, Ma Y, Waitkus MS, Kirsch DG
2023
Preclinical Evaluation of the ATR inhibitor BAY 1895344 as a Radiosensitizer for Head and Neck Squamous Cell Carcinoma
Odhiambo DA, Pittman AN, Rickard AG, Castillo RJ, Bassil AM, Chen J, Ravotti ML, Xu ES, Himes JE, Daniel AR, Watts TL, Williams NT, Luo L, Kirsch DG, Mowery YM
International journal of radiation oncology, biology, physics 2023
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009

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