ResearchIn-Press PreviewCell biologyOncology
Open Access |
10.1172/jci.insight.172506
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Albain, K. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Wyatt, D. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Zlobin, A. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Hilsenbeck, S. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Czerlanis, C. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Peiffer, D. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Convington, K. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Godellas, C. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Lo, S. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Robinson, P. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Czaplicki, K. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Busby, B. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Bova, D. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Tang, P. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Stiff, P. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Fuqua, S. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Miele, L. in: PubMed | Google Scholar
1Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, United States of America
2Department of Cancer Biology, Loyola University Chicago, Maywood, United States of America
3Baylor College of Medicine, Houston, United States of America
4University of Wisconsin Health, Madison, United States of America
5Department of Medicine, University of Chicago, Chicago, United States of America
6Department of Surgery, Division of Surgical Oncology, Ascension Medical Group Illinois, Elk Grove Village, United States of America
7RUSH MD Anderson Cancer Center, Rush University Medical Center, Chicago, United States of America
8Department of Medicine (Hematology and Oncology), Northwestern University, Chicago, United States of America
9Department of Radiology, Loyola University Chicago Stritch School of Medicine, Maywood, United States of America
10Division of Surgical Pathology, Cook County Health, Chicago, United States of America
11Department of Microbiology, Genetics and Immunology, Louisiana State University Health Sciences Center and LSU-LCMC Health Cancer Center, New Orleans, United States of America
Find articles by Osipo, C. in: PubMed | Google Scholar
Published September 29, 2026 - More info
Resistance to endocrine therapy (ET) in ER+ breast cancer is mediated by Notch signaling, but the clinical application of anti-Notch therapy has been limited by the lack of predictive biomarkers. To identify Notch-regulated biomarkers, we conducted a pre-surgical window study evaluating ET combined with the γ-secretase inhibitor (GSI) MK-0752. RNA expressions in tumors were measured using an Affymetrix array and by real-time PCR. ET plus GSI showed more genes were decreased than ET alone. Specifically, DAXX, NOXA, and LFNG RNAs were increased, while fifteen additional transcripts were decreased. Mechanistically, GSI reduced Notch1 occupancy at CSL-binding elements within HES1, HEY2, HEYL, CCND1, MKI67, and DAXX genes, and inhibited cancer stem cells (CSCs) by 90% to 100%. This anti-CSC effect required DAXX, while GSI treatment or Notch1/4 knockdown increased DAXX expression, suggesting transcriptional repression by Notch. Using mouse tumor xenograft studies, ET plus MK-0752 resulted in complete regression of MCF-7 tumors, with DAXX-high tumors showing greater treatment sensitivity. Clinically, high DAXX expression was associated with improved recurrence-free and overall survival. This study found that anti-Notch plus ET in ER+ breast cancer inhibits cancer stem cells by increasing DAXX, a promising predictive biomarker. These findings support clinical evaluation of therapies that increase DAXX expression.