Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

作     者：Jialin Zhang Gengshen Yin Chunmiao Ye Man Feng Changhua Ji Wenzhong Zhou Fei Wang Lixiang Yu Shuya Huang Zhigang Yu Jialin Zhang;Gengshen Yin;Chunmiao Ye;Man Feng;Changhua Ji;Wenzhong Zhou;Fei Wang;Lixiang Yu;Shuya Huang;Zhigang Yu

作者机构：Department of Breast Surgerythe Second Hospital of Shandong UniversityJinan 250033China Institute of Translational Medicine of Breast Disease Prevention and TreatmentShandong UniversityJinan 250033China Shandong Provincial Engineering Laboratory of Translational Research on Prevention and Treatment of Breast DiseaseJinan 250033China Department of Pathologythe Third Affiliated Hospital of Shandong First Medical University(Affiliated Hospital of Shandong Academy of Medical Sciences)Jinan 250031China Department of Pathologythe Second Hospital of Shandong UniversityJinan 250033China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2024年第36卷第2期

页      面：124-137页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (No. 82072914) the Special Foundation for Taishan Scholars and the Fundamental Research Funds for the Central Universities (No. 2022JC009) 

主　　题：Breast cancer HER2 pyrotinib trastuzumab primary resistance pertuzumab 

摘      要：Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is ***: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to ***: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft ***: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance