Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer

Yanjing Li; Yiping He; William Butler; Lingfan Xu; Yan Chang; Kefeng Lei; Hong Zhang; Yinglu Zhou; Allen C. Gao; Qingfu Zhang; Daniel G. Taylor; Donghui Cheng; Suzette Farber-Katz; Rachid Karam; Tyler Landrith; Bing Li; Sitao Wu; Vickie Hsuan; Qing Yang; Hailiang Hu; Xufeng Chen; Melissa Flowers; Shannon J. McCall; John K. Lee; Bryan A. Smith; Jung Wook Park; Andrew S. Goldstein; Owen N. Witte; Qianben Wang; Matthew B. Rettig; Andrew J. Armstrong; Qing Cheng; Jiaoti Huang

doi:10.1126/scitranslmed.aax0428

Research ArticleCancer

Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer

View ORCID ProfileYanjing Li¹,
View ORCID ProfileYiping He¹,
View ORCID ProfileWilliam Butler¹,
Lingfan Xu¹,²,
Yan Chang¹,³,
View ORCID ProfileKefeng Lei¹,⁴,
View ORCID ProfileHong Zhang¹,
View ORCID ProfileYinglu Zhou¹,
Allen C. Gao⁵,
View ORCID ProfileQingfu Zhang¹,⁶,
View ORCID ProfileDaniel G. Taylor⁷,
Donghui Cheng⁸,
View ORCID ProfileSuzette Farber-Katz⁹,
View ORCID ProfileRachid Karam⁹,
Tyler Landrith⁹,
View ORCID ProfileBing Li⁹,
View ORCID ProfileSitao Wu⁹,
View ORCID ProfileVickie Hsuan⁹,
View ORCID ProfileQing Yang¹⁰,
View ORCID ProfileHailiang Hu¹,
View ORCID ProfileXufeng Chen¹,
View ORCID ProfileMelissa Flowers¹,
View ORCID ProfileShannon J. McCall¹,
John K. Lee¹¹,¹²,
Bryan A. Smith⁸,
View ORCID ProfileJung Wook Park⁸,
View ORCID ProfileAndrew S. Goldstein⁷,¹³,¹⁴,
View ORCID ProfileOwen N. Witte⁸,¹³,¹⁵,
View ORCID ProfileQianben Wang¹,
View ORCID ProfileMatthew B. Rettig¹¹,¹⁴,¹⁶,
View ORCID ProfileAndrew J. Armstrong¹⁷,
View ORCID ProfileQing Cheng¹⁸,* and
View ORCID ProfileJiaoti Huang ¹,*

¹Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.
²Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
³Department of Pharmacology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
⁴General Surgery, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Zhejiang 310014, China.
⁵Department of Urology and Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95616, USA.
⁶Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110122, China.
⁷Department of Molecular, Cellular, Developmental Biology, University of California, Los Angeles, CA 90095, USA.
⁸Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁹Ambry Genetics, Aliso Viejo, CA 92656, USA.
¹⁰School of Nursing, Duke University, Durham, NC 27710, USA.
¹¹Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹²Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹³Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁴Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁵Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁶VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
¹⁷Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
¹⁸Department of Surgery, Duke University School of Medicine, Durham NC27710, USA.

↵*Corresponding author. Email: jiaoti.huang{at}duke.edu (J.H.); q.cheng{at}duke.edu (Q.C.)

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Science Translational Medicine 04 Dec 2019:
Vol. 11, Issue 521, eaax0428
DOI: 10.1126/scitranslmed.aax0428

Yanjing Li

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Yiping He

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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William Butler

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Lingfan Xu

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

2Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.

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Yan Chang

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

3Department of Pharmacology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.

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Kefeng Lei

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

4General Surgery, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Zhejiang 310014, China.

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Hong Zhang

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Yinglu Zhou

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Allen C. Gao

5Department of Urology and Cancer Center, University of California Davis School of Medicine, Sacramento, CA 95616, USA.

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Qingfu Zhang

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

6Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110122, China.

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Daniel G. Taylor

7Department of Molecular, Cellular, Developmental Biology, University of California, Los Angeles, CA 90095, USA.

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Donghui Cheng

8Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Suzette Farber-Katz

9Ambry Genetics, Aliso Viejo, CA 92656, USA.

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Rachid Karam

9Ambry Genetics, Aliso Viejo, CA 92656, USA.

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Tyler Landrith

9Ambry Genetics, Aliso Viejo, CA 92656, USA.

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Bing Li

9Ambry Genetics, Aliso Viejo, CA 92656, USA.

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Sitao Wu

9Ambry Genetics, Aliso Viejo, CA 92656, USA.

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Vickie Hsuan

9Ambry Genetics, Aliso Viejo, CA 92656, USA.

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Qing Yang

10School of Nursing, Duke University, Durham, NC 27710, USA.

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Hailiang Hu

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Xufeng Chen

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Melissa Flowers

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Shannon J. McCall

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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John K. Lee

11Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

12Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Bryan A. Smith

8Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Jung Wook Park

8Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Andrew S. Goldstein

7Department of Molecular, Cellular, Developmental Biology, University of California, Los Angeles, CA 90095, USA.

13Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.

14Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Owen N. Witte

8Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

13Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.

15Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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Qianben Wang

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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Matthew B. Rettig

11Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

14Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

16VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.

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Andrew J. Armstrong

17Division of Medical Oncology, Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.

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Qing Cheng

18Department of Surgery, Duke University School of Medicine, Durham NC27710, USA.

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For correspondence: jiaoti.huang@duke.edu q.cheng@duke.edu

Jiaoti Huang

1Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA.

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For correspondence: jiaoti.huang@duke.edu q.cheng@duke.edu

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Targeting cellular heterogeneity with CXCR2 blockade for the treatment of therapy-resistant prostate cancer

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