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Peer-reviewedCC BY 4.0Cells

BORIS in Hormone-Driven Cancers: Epigenetic Reprogramming, Transcriptional Plasticity, and Therapeutic Implications

  • Sara Saleem1,2
  • Luke Gaughan1
  • Craig N. Robson1
  1. 1Newcastle University Centre for Cancer, Paul O’Gorman Building, Newcastle upon Tyne NE2 4AD, UK
  2. 2Faculty of Biomedical Sciences, University of Benghazi, Benghazi P.O. Box 1308, Libya
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Abstract

Hormone-driven cancers, including prostate, breast, endometrial and ovarian cancers, are a leading cause of cancer-related mortality. Endocrine therapies targeting androgen receptor and oestrogen receptor/progesterone receptor signalling have improved outcomes, but acquired resistance arising through genetic and epigenetic mechanisms that bypass receptor dependence remains a major challenge. BORIS (Brother of the Regulator of Imprinted Sites), a CTCF paralogue, is a germline-restricted regulator that becomes aberrantly reactivated in cancer through promoter hypomethylation, p53 loss, and loss of CTCF-mediated repression. Once expressed, BORIS occupies CTCF sites, displacing or co-occupying them with CTCF, and reprograms clustered sites into alternative transcriptional start sites through SRCAP-mediated H2A.Z deposition, activating germline genes that sustain proliferation, and therapeutic resistance. BORIS expression correlates with poor prognosis in ovarian and endometrial cancers, associates with ER/PR levels in breast cancer, and correlates with Gleason score in prostate cancer. BORIS represses AR signalling in ovarian cancer and inversely correlates with receptor expression in endometrial cancer. Its cancer-testis antigen properties position BORIS as an immunotherapy target, with preclinical vaccine efficacy demonstrated in breast cancer models. This review synthesises the disease-specific evidence positioning BORIS as a driver of transcriptional reprogramming and endocrine resistance, identifies current knowledge gaps, and discusses translational implications of targeting this pathway.

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Cite

BibTeXRIS
BibTeX
@article{saleem2026boris,
  title = {{BORIS in Hormone-Driven Cancers: Epigenetic Reprogramming, Transcriptional Plasticity, and Therapeutic Implications}},
  author = {Sara Saleem and Luke Gaughan and Craig N. Robson},
  journal = {Cells},
  year = {2026},
  month = nov,
  doi = {10.3390/cells15212001},
  url = {https://www.mdpi.com/2073-4409/15/21/2001},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - BORIS in Hormone-Driven Cancers: Epigenetic Reprogramming, Transcriptional Plasticity, and Therapeutic Implications
AU  - Sara Saleem
AU  - Luke Gaughan
AU  - Craig N. Robson
PY  - 2026
DA  - 2026/11/03
JO  - Cells
DO  - 10.3390/cells15212001
UR  - https://www.mdpi.com/2073-4409/15/21/2001
AB  - Hormone-driven cancers, including prostate, breast, endometrial and ovarian cancers, are a leading cause of cancer-related mortality. Endocrine therapies targeting androgen receptor and oestrogen receptor/progesterone receptor signalling have improved outcomes, but acquired resistance arising through genetic and epigenetic mechanisms that bypass receptor dependence remains a major challenge. BORIS (Brother of the Regulator of Imprinted Sites), a CTCF paralogue, is a germline-restricted regulator that becomes aberrantly reactivated in cancer through promoter hypomethylation, p53 loss, and loss of CTCF-mediated repression. Once expressed, BORIS occupies CTCF sites, displacing or co-occupying them with CTCF, and reprograms clustered sites into alternative transcriptional start sites through SRCAP-mediated H2A.Z deposition, activating germline genes that sustain proliferation, and therapeutic resistance. BORIS expression correlates with poor prognosis in ovarian and endometrial cancers, associates with ER/PR levels in breast cancer, and correlates with Gleason score in prostate cancer. BORIS represses AR signalling in ovarian cancer and inversely correlates with receptor expression in endometrial cancer. Its cancer-testis antigen properties position BORIS as an immunotherapy target, with preclinical vaccine efficacy demonstrated in breast cancer models. This review synthesises the disease-specific evidence positioning BORIS as a driver of transcriptional reprogramming and endocrine resistance, identifies current knowledge gaps, and discusses translational implications of targeting this pathway.
SN  - 2073-4409
ER  -