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Dysregulated gene expression is a hallmark of the pathogenesis and progression of various cancers, including the triple-negative breast cancer (TNBC) subtype. We previously demonstrated that knockout of the deubiquitinase USP19 reduces tumor cell migration and invasion in TNBC models. Building on this evidence, we developed a computational strategy for drug repurposing that identified several approved compounds capable of mimicking the transcriptional signature of USP19 knockout in the MDA-MB-231 breast cancer cell line and may offer novel therapeutic alternatives to inhibit metastasis. This analysis revealed several candidate compounds, such as rituximab, Torin-1, CCL16, FK866, and eflornithine, with strong transcriptional similarity and prior evidence of antitumor activity.

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In silico Repurposing Screen to Identify Compounds with Anti-metastatic Potential in Breast Cancer Cell Line

  • 会议论文

  • 发表日期：

    2025年

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  • Camila Contestabile Monti,
  • Agustina Verschoor,
  • Mario Rossi,
  • Ignacio Cassol

摘要

Dysregulated gene expression is a hallmark of the pathogenesis and progression of various cancers, including the triple-negative breast cancer (TNBC) subtype. We previously demonstrated that knockout of the deubiquitinase USP19 reduces tumor cell migration and invasion in TNBC models. Building on this evidence, we developed a computational strategy for drug repurposing that identified several approved compounds capable of mimicking the transcriptional signature of USP19 knockout in the MDA-MB-231 breast cancer cell line and may offer novel therapeutic alternatives to inhibit metastasis. This analysis revealed several candidate compounds, such as rituximab, Torin-1, CCL16, FK866, and eflornithine, with strong transcriptional similarity and prior evidence of antitumor activity.