Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, 3584 Utrecht, the Netherlands.
Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Cell Rep Med. 2023 Oct 17;4(10):101203. doi: 10.1016/j.xcrm.2023.101203. Epub 2023 Oct 3.
Patients with early-stage HER2-overexpressing breast cancer struggle with treatment resistance in 20%-40% of cases. More information is needed to predict HER2 therapy response and resistance in vivo. In this study, we perform (phospho)proteomics analysis of pre-treatment HER2 needle biopsies of early-stage invasive breast cancer to identify molecular signatures predictive of treatment response to trastuzumab, pertuzumab, and chemotherapy. Our data show that accurate quantification of the estrogen receptor (ER) and HER2 biomarkers, combined with the assessment of associated biological features, has the potential to enable better treatment outcome prediction. In addition, we identify cellular mechanisms that potentially precondition tumors to resist therapy. We find proteins with expression changes that correlate with resistance and constitute to a strong predictive signature for treatment success in our patient cohort. Our results highlight the multifactorial nature of drug resistance in vivo and demonstrate the necessity of deep tumor profiling.
早期 HER2 过表达乳腺癌患者中有 20%-40%存在治疗抵抗。为了预测体内 HER2 治疗反应和耐药性，需要更多的信息。在这项研究中，我们对早期浸润性乳腺癌的 HER2 针吸活检标本进行（磷酸化）蛋白质组学分析，以确定预测曲妥珠单抗、帕妥珠单抗和化疗治疗反应的分子特征。我们的数据表明，准确定量雌激素受体 (ER) 和 HER2 生物标志物，并结合相关生物学特征的评估，有可能实现更好的治疗结果预测。此外，我们还发现了可能使肿瘤对治疗产生耐药的细胞机制。我们发现与耐药性相关的表达变化的蛋白质，并构成了我们患者队列中治疗成功的强烈预测特征。我们的研究结果突出了体内药物耐药的多因素性质，并证明了深入的肿瘤分析的必要性。
