NF-κB associated markers of prognosis in early and metastatic triple negative breast cancer.

Autor: De La Cruz P; Pathobiology Graduate Program, Brown University, Providence, Rhode Island, USA.; Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, Providence, Rhode Island, USA., McAdams J; Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, Providence, Rhode Island, USA., Morales Aquino M; School of Public Health, Brown University, Providence, Rhode Island, USA., Fernandez AI; Caris Life Sciences, Inc., Phoenix, AZ, USA., Elliott A; Caris Life Sciences, Inc., Phoenix, AZ, USA., Lustberg M; Yale Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA., Schorl C; Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University Providence, Providence, Rhode Island, USA., Ribeiro JR; Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, Providence, Rhode Island, USA.; Department of Obstetrics and Gynecology Warren-Alpert Medical School of Brown University, Providence, Rhode Island, USA., James NE; Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, Providence, Rhode Island, USA. nejames@carene.org.; Department of Obstetrics and Gynecology Warren-Alpert Medical School of Brown University, Providence, Rhode Island, USA. nejames@carene.org.; Department of Obstetrics and Gynecology, Program in Women's Oncology, Women and Infants Hospital, 200 Chestnut Street, Room 208, Providence, Rhode Island, 02903, USA. nejames@carene.org.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2024 Dec 02; Vol. 26 (1), pp. 175. Date of Electronic Publication: 2024 Dec 02.
DOI: 10.1186/s13058-024-01925-3
Abstrakt: Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. While PD-1 based immunotherapies overall have led to improved treatment outcomes for this disease, a diverse response to frontline chemotherapy and immunotherapy still exist in TNBC, highlighting the need for more robust prognostic markers.
Methods: Tumor-intrinsic immunotranscriptomics, serum cytokine profiling, and tumor burden studies were conducted in two syngeneic mouse models to assess differential effects in both the early-stage and metastatic setting. Bioinformatic analyses of both early and metastatic TNBC patient data were performed to assess if identified NF-κB-associated factors are associated with improved patient clinical outcomes.
Results: NF-κB signaling driven by lymphotoxin beta expression is associated with tumor regression in TNBC mouse models. Furthermore, lymphotoxin beta expression in patient TNBC cohorts is prognostic of improved survival outcomes.
Conclusions: This study highlights the potential role for NF-κB-associated factors, specifically lymphotoxin beta to be used as prognostic markers in TNBC, which could ultimately provide insight for improved targeted treatment approaches in the clinic.
Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in compliance with guidelines of the Declaration of Helsinki, Belmont report, and U.S. Common rule. Analysis of human patient data was performed utilizing retrospective, deidentified clinical data. All animal protocols were approved by the Brown University Animal Care and Use Committee (#22-09-0002) and were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. All animal protocols were reviewed and acknowledged by the Lifespan University Institutional Care and Use Committee (#1987412-1). Consent for publication: Not applicable. Competing interests: JRR is currently an employee at Caris Life Sciences however, her she was an employee of Women and Infants Hospital at the time this research was conducted. All other authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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