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<p>Oesophageal adenocarcinoma (OAC) and its precursor condition, Barrett oesophagus, are characterized by phenotypic and molecular intertumoural and intratumoural heterogeneity. This heterogeneity arises in space and time through a complex and still poorly understood interplay between cancer-cell-intrinsic factors, the tumour microenvironment and external influences, such as exposure to anticancer therapies. Together, these elements contribute to a high degree of resistance to therapy while limiting the development of novel targeted therapies and the identification of predictive biomarkers. This situation is exacerbated both in Barrett oesophagus and OAC by a historical clinical reliance on biopsy samples that reflect disease status only at a single location and timepoint. A better understanding of heterogeneity is therefore vital to improve efforts to intercept the development of and optimize treatments for OAC. In this Review, we provide an overview of current and future directions of research on the heterogeneity of Barrett oesophagus and OAC, summarizing our knowledge of the factors that influence heterogeneity, and its consequences across the spectrum of these diseases.</p>

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The biology and therapeutic implications of heterogeneity in Barrett oesophagus and oesophageal adenocarcinoma

  • 期刊论文

  • 发表日期：

    2025年11月11日

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  • Dylan P. McClurg,
  • Sally Pan,
  • Rebecca C. Fitzgerald,
  • Christopher M. Jones

摘要

Oesophageal adenocarcinoma (OAC) and its precursor condition, Barrett oesophagus, are characterized by phenotypic and molecular intertumoural and intratumoural heterogeneity. This heterogeneity arises in space and time through a complex and still poorly understood interplay between cancer-cell-intrinsic factors, the tumour microenvironment and external influences, such as exposure to anticancer therapies. Together, these elements contribute to a high degree of resistance to therapy while limiting the development of novel targeted therapies and the identification of predictive biomarkers. This situation is exacerbated both in Barrett oesophagus and OAC by a historical clinical reliance on biopsy samples that reflect disease status only at a single location and timepoint. A better understanding of heterogeneity is therefore vital to improve efforts to intercept the development of and optimize treatments for OAC. In this Review, we provide an overview of current and future directions of research on the heterogeneity of Barrett oesophagus and OAC, summarizing our knowledge of the factors that influence heterogeneity, and its consequences across the spectrum of these diseases.