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<p>While many Antibody Drug Conjugates (ADCs) are investigated in solid tumors, their target expression and heterogeneity is poorly documented in metastatic breast cancer. Here, we perform RNA sequencing to investigate expression of 72 ADC targets in 909 samples from 30 female patients from our post-mortem tissue donation program UPTIDER (NCT04531696). We report that the highest median expression in metastases is seen for <i>FN1, MUC1, LAMP1, HER3</i> and <i>SLC39A6</i>. <i>TROP2</i> and <i>HER2</i> have the 9<sup>th</sup> and 27<sup>th</sup> highest expression. We observe reduced expression in metastases as compared to primary untreated tumors for 15 targets but observe only limited differences in expression between metastases of different subtypes. We show that <i>TROP2</i>, <i>VTCN1</i>, <i>NECTIN4</i>, <i>HER2</i> and <i>HER3</i> are interesting targets as they have higher mRNA expression in tumor as compared to normal tissues. This is confirmed at the protein level by explorative immunohistochemistry. Correlations between targets can help guide design of bispecific ADCs. Taken together, the results of this study can help inform the design and prioritization of drugs for the treatment of patients with metastatic breast cancer.</p>

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Expression of antibody-drug conjugate targets in post-mortem samples of breast cancer metastases and normal tissue

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月26日

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  • Kristien Borremans,
  • Anirudh Pabba,
  • Gitte Zels,
  • Amena Mahdami,
  • Camille Carette,
  • Marion Maetens,
  • Karen Van Baelen,
  • Josephine Van Cauwenberge,
  • Ha Linh Nguyen,
  • Hava Izci,
  • Sophia Leduc,
  • Sigrid Hatse,
  • Madita Nysen,
  • Bram Boeckx,
  • Evy Vanderheyden,
  • Thomas Van Brussel,
  • Françoise Derouane,
  • Kevin Punie,
  • Wouter Van Den Bogaert,
  • Peter Vermeulen,
  • Elia Biganzoli,
  • Diether Lambrechts,
  • Patrick Neven,
  • Hans Wildiers,
  • Giuseppe Floris,
  • François Richard,
  • Christine Desmedt

摘要

While many Antibody Drug Conjugates (ADCs) are investigated in solid tumors, their target expression and heterogeneity is poorly documented in metastatic breast cancer. Here, we perform RNA sequencing to investigate expression of 72 ADC targets in 909 samples from 30 female patients from our post-mortem tissue donation program UPTIDER (NCT04531696). We report that the highest median expression in metastases is seen for FN1, MUC1, LAMP1, HER3 and SLC39A6. TROP2 and HER2 have the 9th and 27th highest expression. We observe reduced expression in metastases as compared to primary untreated tumors for 15 targets but observe only limited differences in expression between metastases of different subtypes. We show that TROP2, VTCN1, NECTIN4, HER2 and HER3 are interesting targets as they have higher mRNA expression in tumor as compared to normal tissues. This is confirmed at the protein level by explorative immunohistochemistry. Correlations between targets can help guide design of bispecific ADCs. Taken together, the results of this study can help inform the design and prioritization of drugs for the treatment of patients with metastatic breast cancer.