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<p>Triple-negative breast cancer (TNBC) lacks durable, broadly applicable molecular targets, and therapeutic decision-making increasingly depends on biomarkers that can support patient selection and adaptive treatment. Trophoblast cell-surface antigen 2 (TROP2; encoded by <i>TACSTD2</i>) is frequently expressed in TNBC and is an established therapeutic target, yet tissue-based assessment is limited by sampling bias, intratumoural and intermetastatic heterogeneity, and the inability to monitor longitudinal changes during treatment. In this review, we synthesize published evidence supporting TROP2 as (i) a biologically relevant marker associated with aggressive TNBC phenotypes and (ii) a phenotypic target suitable for noninvasive whole-body quantification. We examine the emerging rationale for TROP2-targeted positron emission tomography/computed tomography PET/CT as a potential companion diagnostic, mapping spatial heterogeneity across the full disease burden, enabling serial assessment of target dynamics under therapeutic pressure, and informing treatment sequencing when target availability changes. We propose a hypothesis-generating integrative framework linking <i>TACSTD2</i> transcriptomic signals, immunohistochemistry scoring, and quantitative PET metrics, and we outline key requirements for clinical translation, including assay harmonization, imaging standardization, and validation strategies that connect PET readouts to clinical outcomes. Positioning TROP2 imaging as a functional measure of target availability may strengthen precision use of TROP2-directed therapies and accelerate the development of TROP2-based theranostic approaches in TNBC, pending prospective validation.</p>

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TROP2-targeted PET in triple-negative breast cancer: integrating TACSTD2 genomics and immunohistochemistry for companion diagnostic development

  • 期刊论文

  • 发表日期：

    2026年4月8日

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  • Tshimogo T. Sathekge,
  • Joseph Kabunda,
  • Joseph Chalwe,
  • Mankgopo Kgatle,
  • Frederik Cleeren,
  • Mike Sathekge

摘要

Triple-negative breast cancer (TNBC) lacks durable, broadly applicable molecular targets, and therapeutic decision-making increasingly depends on biomarkers that can support patient selection and adaptive treatment. Trophoblast cell-surface antigen 2 (TROP2; encoded by TACSTD2) is frequently expressed in TNBC and is an established therapeutic target, yet tissue-based assessment is limited by sampling bias, intratumoural and intermetastatic heterogeneity, and the inability to monitor longitudinal changes during treatment. In this review, we synthesize published evidence supporting TROP2 as (i) a biologically relevant marker associated with aggressive TNBC phenotypes and (ii) a phenotypic target suitable for noninvasive whole-body quantification. We examine the emerging rationale for TROP2-targeted positron emission tomography/computed tomography PET/CT as a potential companion diagnostic, mapping spatial heterogeneity across the full disease burden, enabling serial assessment of target dynamics under therapeutic pressure, and informing treatment sequencing when target availability changes. We propose a hypothesis-generating integrative framework linking TACSTD2 transcriptomic signals, immunohistochemistry scoring, and quantitative PET metrics, and we outline key requirements for clinical translation, including assay harmonization, imaging standardization, and validation strategies that connect PET readouts to clinical outcomes. Positioning TROP2 imaging as a functional measure of target availability may strengthen precision use of TROP2-directed therapies and accelerate the development of TROP2-based theranostic approaches in TNBC, pending prospective validation.