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Case series exploring hormonal sensitivity in prostate cancer patients harboring the germline African-ancestry HOXB13 X285K variant

Prostate Cancer and Prostatic Diseases (2025)Cite this article

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Abstract

Background

Recently, a germline HOXB13 variant, X285K was identified as a risk factor for prostate cancer in men of African ancestry. While this variant is likely associated with more aggressive prostate cancer, there has not yet been an in-depth clinical description of individual patients carrying this variant and their response to systemic therapies.

Methods

We studied six cases of germline X285K carriers with metastatic hormone-sensitive prostate cancer to characterize their hormonal sensitivity or resistance.

Conclusions

Longitudinal outcome analysis indicates that patients carrying X285K generally show favorable responses to therapies targeting the androgen receptor (AR), a finding that requires confirmation.

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Fig. 1: The clinical course of X285K-carrier patients.

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Acknowledgements

The generous support from the Patrick C Walsh Hereditary Prostate Cancer Program, Prostate Cancer Foundation Young Investigator Award, and the Ambrose Monell Foundation is gratefully acknowledged. The authors would like to thank Dr. Claire de la Calle (Department of Urology, University of Washington) for her assistance with English-French interpretation throughout the collaboration with the University Hospital of Martinique. The figure was created in BioRender.

Funding

The study was supported by the Patrick C Walsh Hereditary Prostate Cancer program.

Author information

Authors and Affiliations

  1. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Mayuko Kanayama, Changxue Lu, William B. Isaacs & Jun Luo

  2. Department of Molecular Cancer Genetic, University Hospital of Martinique, Fort de France, France

    Emeline Colomba & Régine Marlin

  3. Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA

    Yusra Shao

  4. Labcorp (formerly Invitae Corp.), San Francisco, CA, USA

    Sarah M. Nielsen & Edward D. Esplin

  5. Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

    John C. Henegan

  6. Mayo Clinic Comprehensive Cancer Center, Rochester, MN, USA

    Elisabeth I. Heath

  7. Department of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Emmanuel S. Antonarakis

Authors
  1. Mayuko Kanayama
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  2. Emeline Colomba
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  3. Yusra Shao
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  4. Sarah M. Nielsen
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  5. Edward D. Esplin
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  6. Changxue Lu
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  7. William B. Isaacs
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  11. Régine Marlin
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Contributions

CL performed experiments. MK, EC, YS, SMN, EDE, JCH, EIH, RM and ESA collected and reviewed patient treatment data. MK wrote the original draft. JCH, EIH, RM, JL, ESA, and WBI revised and finalized the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jun Luo, Régine Marlin or Emmanuel S. Antonarakis.

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Competing interests

JL has served as a paid consultant/advisor for Sun Pharma, received research funding for his institution from Sanofi, Constellation, Calibr, AstraZeneca, and Cardiff Oncology, and is the lead inventor of AR-V7-related technologies owned by Johns Hopkins University and licensed to Qiagen and A&G. CL is the co-inventor of AR-V7-related technologies owned by JHU and licensed to Qiagen and A&G. SMN and EDE are employees of Labcorp (formerly Invitae Corp.). EDE is a scientific advisory board member and stockholder of Taproot Health, Exir Bio and ROMTech. WBI is a co-inventor on a patent (no. 9593380; Johns Hopkins Univ.) related to the discovery of HOXB13 as a prostate cancer susceptibility gene. WBI, MK, and JL are co-inventors on a patent (PCT/US2023/075775) filed by the Johns Hopkins University related to HOXB13 X285K as a biomarker and therapeutic target. ESA has served as a paid consultant/advisor for Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, and received an honorarium from Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma, Merck, AstraZeneca, Clovis Oncology. ESA received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, as well as travel accommodations from Sanofi, Dendreon, and Medivation. ESA is a co-inventor of a technology owned by Johns Hopkins University and licensed to Qiagen and A&G.

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Kanayama, M., Colomba, E., Shao, Y. et al. Case series exploring hormonal sensitivity in prostate cancer patients harboring the germline African-ancestry HOXB13 X285K variant. Prostate Cancer Prostatic Dis (2025). https://doi.org/10.1038/s41391-025-00994-5

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  • DOI: https://doi.org/10.1038/s41391-025-00994-5

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