title: Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.
abstract: In the era of new and mostly effective molecular targeted therapies, human epidermal growth factor receptor 2 positive (HER2+) cancers are still intractable diseases. Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 tyrosine kinase inhibitor, has greatly improved breast cancer prognosis in recent years after the initial introduction of trastuzumab (Herceptin). However, clinical evidence indicates the existence of both primary unresponsiveness and secondary lapatinib resistance, which leads to the failure of this agent in HER2+ cancer patients. It remains a major clinical challenge to target the oncogenic pathways with drugs having low resistance. Multiple pathways are involved in the occurrence of lapatinib resistance, including the pathways of receptor tyrosine kinase, non-receptor tyrosine kinase, autophagy, apoptosis, microRNA, cancer stem cell, tumor metabolism, cell cycle, and heat shock protein. Moreover, understanding the relationship among these mechanisms may contribute to future tumor combination therapies. Therefore, it is of urgent necessity to elucidate the precise mechanisms of lapatinib resistance and improve the therapeutic use of this agent in clinic. The present review, in the hope of providing further scientific support for molecular targeted therapies in HER2+ cancers, discusses about the latest findings and new concepts on molecular mechanisms underlying lapatinib resistance.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Xiangcheng People's Hospital, Suzhou, Jiangsu Province, 215131, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. strexboy@163.com.
authors.forename: Qiaoming
authors.initials: Q
authors.lastname: Zhi
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China. jiangmin1023@suda.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
keywords: Breast cancer; Drug resistance; Gastric cancer; Lapatinib; Targeted therapy