Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention

Stem Cell Rev Rep. 2026 Feb;22(2):767-802. doi: 10.1007/s12015-025-11029-w. Epub 2025 Dec 9.

Abstract

All cells within an organism share identical genetic material, yet epigenetic mechanisms determine stem cell fate by precisely regulating transcriptional programs. Histone acetylation is a key epigenetic modification that establishes an open chromatin structure, which is recognized by proteins involved in modulating chromatin dynamics essential for stem cell functions. Bromodomain (BrD)-containing proteins specifically recognize acetylated lysines on histones and act as critical epigenetic regulators within larger protein complexes. This review comprehensively describes the BrD protein family, highlighting their structural classifications and diverse functions, and explores their critical roles in regulating stem cell pluripotency and differentiation, and their implications in cancer development. Dysregulated BrD proteins can drive cancer by increasing stem cell-like features and tumor heterogeneity, making them a potential target for cancer treatment. Furthermore, this review emphasizes BrD inhibitors as promising therapeutic targets capable of targeting cancer stem cells and potentially mitigating cancer progression. Understanding the detailed functions and regulatory pathways of BrD proteins may open new avenues for improved cancer stem cell-targeted therapies.

Keywords: Bromodomain; Bromodomain inhibitors; Cancer stem cells; Epigenetic regulators; Histone acetylation.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Animals
  • Cell Differentiation
  • Epigenesis, Genetic
  • Histones / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • Histones