Luz Paulo, Ramos Sofia, Oliveira Maria José, Costa João G, Saraiva Nuno, Fernandes Ana S
CBIOS, Universidade Lusófona's Research Center for Biosciences & Health Technologies, Lisbon, Portugal; Universidad de Alcalá de Henares. Departamento de Ciencias Biomédicas, Alcalá de Henares, Madrid, Spain; Medical Oncology Department, Unidade Local de Saúde do Baixo Alentejo - Hospital José Joaquim Fernandes, Beja, Portugal.
CBIOS, Universidade Lusófona's Research Center for Biosciences & Health Technologies, Lisbon, Portugal; Universidad de Alcalá de Henares. Departamento de Ciencias Biomédicas, Alcalá de Henares, Madrid, Spain.
Redox Biol. 2025 May;82:103609. doi: 10.1016/j.redox.2025.103609. Epub 2025 Mar 22.
In HER2+ breast cancer (BC), neoadjuvant therapy represents an ideal scenario for translational research, considering pathological complete response (pCR) as an endpoint. In these patients, achieving pCR after neoadjuvant therapy is associated with a better prognosis. However, biomarkers are needed to tailor optimal treatment for each patient. Evaluating tumour-infiltrating lymphocytes (TILs) has gained attention in predicting pCR. In the context of metastatic disease, TILs also appear to play a role in predicting outcomes. The interaction between the presence of TILs and reactive oxygen species (ROS) remains an area to be explored. ROS are critical for tumour cell homeostasis, and different levels can trigger differential biological responses in cancer cells and their microenvironment. Nevertheless, the influence of ROS on treatment efficacy and prognosis in patients with HER2+ BC remains to be elucidated. In this article, we reviewed the interplay between treatment response, immune system activation, and ROS production in HER2+ BC and suggested novel areas of intervention and research. We also present a bioinformatic analysis demonstrating that the altered expression of several redox-related genes could be associated with the prevalence of immune cell populations in the tumour microenvironment and with patient survival. New biomarkers are thus suggested and should be further explored to tailor the best treatment to each patient.
在人表皮生长因子受体2阳性（HER2+）乳腺癌（BC）中，新辅助治疗以病理完全缓解（pCR）为终点，是转化研究的理想情形。在这些患者中，新辅助治疗后实现pCR与更好的预后相关。然而，需要生物标志物来为每位患者量身定制最佳治疗方案。评估肿瘤浸润淋巴细胞（TILs）在预测pCR方面已受到关注。在转移性疾病的背景下，TILs似乎也在预测预后中发挥作用。TILs的存在与活性氧（ROS）之间的相互作用仍是一个有待探索的领域。ROS对肿瘤细胞内稳态至关重要，不同水平的ROS可在癌细胞及其微环境中引发不同的生物学反应。然而，ROS对HER2+ BC患者治疗疗效和预后的影响仍有待阐明。在本文中，我们综述了HER2+ BC中治疗反应、免疫系统激活和ROS产生之间的相互作用，并提出了新的干预和研究领域。我们还进行了一项生物信息学分析，结果表明几个氧化还原相关基因的表达改变可能与肿瘤微环境中免疫细胞群体的 prevalence 以及患者生存相关。因此，提出了新的生物标志物，应进一步探索以针对每位患者量身定制最佳治疗方案。
