Tumor Biology

, Volume 37, Issue 12, pp 15411–15431 | Cite as

Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms

  • Huiping Shi
  • Weili Zhang
  • Qiaoming Zhi
  • Min Jiang


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.


Lapatinib Drug resistance Breast cancer Gastric cancer Targeted therapy 



This study was supported by a grant from the National Natural Science Foundation of China (no. 81402176), the Natural Science Foundation of Jiangsu Province (no. BK20140288), and the Natural Science Foundation of Jiangsu Higher Education Institutions of China (no. 14KJB320011).

Compliance with ethical standards

Conflicts of interest



1. National Natural Science Foundation of China, No. 81402176

2. Natural Science Foundation of Jiangsu Province, No. BK20140288

3. Natural Science Foundation of Jiangsu Higher Education Institutions of China, No: 14KJB320011


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of GastroenterologyXiangcheng People’s HospitalSuzhouChina
  3. 3.Department of General SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  4. 4.Department of OncologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina

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