Capecitabine Efficacy Is Correlated with TYMP and RB1 Expression in PDX Established from Triple-Negative Breast Cancers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Elisabetta MarangoniFabien Reyal

Abstract

Purpose: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy have a poor outcome. We developed patient-derived xenografts (PDX) from residual tumors to identify efficient chemotherapies and predictive biomarkers in a context of resistance to anthracyclines- and taxanes-based treatments.Experimental Design: PDX were established from residual tumors of primary breast cancer patients treated in neoadjuvant setting. TNBC PDX were treated by anthracyclines, taxanes, platins, and capecitabine. Predictive biomarkers were identified by transcriptomic and immunohistologic analysis. Downregulation of RB1 was performed by siRNA in a cell line established from a PDX.Results: Residual TNBC PDX were characterized by a high tumor take, a short latency, and a poor prognosis of the corresponding patients. With the exception of BRCA1/2-mutated models, residual PDX were resistant to anthracyclines, taxanes, and platins. Capecitabine, the oral prodrug of 5-FU, was highly efficient in 60% of PDX, with two models showing complete responses. Prior treatment of a responder PDX with 5-FU increased expression of thymidylate synthase and decreased efficacy of capecitabine. Transcriptomic and IHC analyses of ...Continue Reading

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Citations

Mar 13, 2019·International Journal of Cancer. Journal International Du Cancer·Florence CoussyElisabetta Marangoni
Mar 27, 2020·Medical Sciences : Open Access Journal·Ugo TestaElvira Pelosi
Feb 23, 2020·Science Translational Medicine·Florence CoussyElisabetta Marangoni
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Mar 6, 2019·Therapeutic Advances in Medical Oncology·Rafael CaparicaMartine Piccart
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Dec 19, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Henry C-H LawNicholas T Woods
Jan 10, 2021·Biomaterials·Weijing HanJacques Camonis
Mar 25, 2021·Cancer Management and Research·Zhitao LiBingqing Hui
Aug 30, 2021·Molecular Cancer·Salvatore BenfattoBalca R Mardin
Sep 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Keke LiangCaius G Radu

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