Abstract

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situHerceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

Original languageEnglish (US)
Article number6609
JournalScientific Reports
Volume4
DOIs
StatePublished - Oct 14 2014

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Drug Receptors
Drug Resistance
Drug Interactions
Mucin-4
Neoplasms
Surface Plasmon Resonance
Treatment Failure
Pharmaceutical Preparations
Membrane Proteins
Monoclonal Antibodies
Breast Neoplasms
Trastuzumab
Therapeutics
human ERBB2 protein
Proteins

ASJC Scopus subject areas

  • General

Cite this

In situ drug-receptor binding kinetics in single cells : A quantitative label-free study of anti-tumor drug resistance. / Wang, Wei; Yin, Linliang; Gonzalez-Malerva, Laura; Wang, Shaopeng; Yu, Xiaobo; Eaton, Seron; Zhang, Shengtao; Chen, Hong Yuan; LaBaer, Joshua; Tao, Nongjian.

In: Scientific Reports, Vol. 4, 6609, 14.10.2014.

Research output: Contribution to journalArticle

Wang, Wei ; Yin, Linliang ; Gonzalez-Malerva, Laura ; Wang, Shaopeng ; Yu, Xiaobo ; Eaton, Seron ; Zhang, Shengtao ; Chen, Hong Yuan ; LaBaer, Joshua ; Tao, Nongjian. / In situ drug-receptor binding kinetics in single cells : A quantitative label-free study of anti-tumor drug resistance. In: Scientific Reports. 2014 ; Vol. 4.
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