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Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
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Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms

Huiping Shi1, Weili Zhang2, Qiaoming Zhi3

  • 1Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|October 12, 2016
PubMed

Insights

Lapatinib resistance is a major challenge in HER2+ cancers. This review explores molecular mechanisms of resistance, including receptor tyrosine kinase and autophagy pathways, to improve targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Human epidermal growth factor receptor 2 positive (HER2+) cancers remain challenging despite advances in molecular targeted therapies.
  • Lapatinib, a dual inhibitor of EGFR and HER2, has improved breast cancer outcomes but faces primary and secondary resistance.
  • Overcoming lapatinib resistance is critical for effective treatment of HER2+ cancers.

Approach:

  • This review synthesizes current research on the molecular mechanisms underlying lapatinib resistance in HER2+ cancers.
  • It examines multiple resistance pathways, including receptor tyrosine kinase, non-receptor tyrosine kinase, autophagy, apoptosis, and microRNA.
  • The review also considers the roles of cancer stem cells, tumor metabolism, cell cycle, and heat shock proteins in resistance.

Key Points:

  • Lapatinib resistance involves complex interactions across various cellular pathways.
  • Understanding these interconnected mechanisms is essential for developing novel therapeutic strategies.
  • Specific pathways implicated include receptor tyrosine kinase signaling, autophagy, and apoptosis.

Conclusions:

  • Elucidating the precise mechanisms of lapatinib resistance is urgently needed to optimize its clinical use.
  • Insights into resistance pathways can guide the development of combination therapies for HER2+ cancers.
  • Further research into molecular mechanisms will support the advancement of targeted therapies for intractable HER2+ cancers.
Keywords:
Breast cancerDrug resistanceGastric cancerLapatinibTargeted therapy

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