Resistance mechanism against trastuzumab in HER2-positive cancer cells and its negation by Src inhibition

Mei Hua Jin, Ah Rong Nam, Ji Eun Park, Ju Hee Bang, Yung Jue Bang, Do-Youn Oh

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Trastuzumab in combination with chemotherapy is the SNU2773HR cell lines. In SNU216HR and SNU2773HR cell standard of care for patients with human epidermal growth lines, phospho-FAK (focal adhesion kinase) was elevated. factor receptor 2 (HER2)-positive breast and gastric cancers. Bosutinib as a Src inhibitor suppressed growth, cell-cycle Several resistance mechanisms against anti-HER2 therapy have progression, and migration in both parental and HR cell lines. been proposed. Src activation has been suggested to be respon-Specifically, Src interacted with FAK to affect downstream sible for the resistance of HER2-positive breast cancer. In our molecules such as AKT, ERK, and STAT3. Bosutinib showed study, we generated four trastuzumab-resistant (HR) cancer more potent antitumor effects in Src-activated HR cell lines cell lines from HER2-amplified gastric and biliary tract cancer than parental cell lines. Taken together, this study suggests cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773). that Src inhibition may be an effective measure to overcome Elevated Src phosphorylation was detected in SNU2670HR trastuzumab resistance in HER2-positive cancer.

Original languageEnglish
Pages (from-to)1145-1154
Number of pages10
JournalMolecular Cancer Therapeutics
Volume16
Issue number6
DOIs
StatePublished - 1 Jun 2017

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Cell Line
Neoplasms
Biliary Tract Neoplasms
Breast Neoplasms
Focal Adhesion Protein-Tyrosine Kinases
Growth Inhibitors
Standard of Care
Combination Drug Therapy
Stomach Neoplasms
Trastuzumab
Stomach
Cell Cycle
Phosphorylation
Growth
bosutinib
Therapeutics

Cite this

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title = "Resistance mechanism against trastuzumab in HER2-positive cancer cells and its negation by Src inhibition",
abstract = "Trastuzumab in combination with chemotherapy is the SNU2773HR cell lines. In SNU216HR and SNU2773HR cell standard of care for patients with human epidermal growth lines, phospho-FAK (focal adhesion kinase) was elevated. factor receptor 2 (HER2)-positive breast and gastric cancers. Bosutinib as a Src inhibitor suppressed growth, cell-cycle Several resistance mechanisms against anti-HER2 therapy have progression, and migration in both parental and HR cell lines. been proposed. Src activation has been suggested to be respon-Specifically, Src interacted with FAK to affect downstream sible for the resistance of HER2-positive breast cancer. In our molecules such as AKT, ERK, and STAT3. Bosutinib showed study, we generated four trastuzumab-resistant (HR) cancer more potent antitumor effects in Src-activated HR cell lines cell lines from HER2-amplified gastric and biliary tract cancer than parental cell lines. Taken together, this study suggests cell lines (SNU-216, NCI-N87, SNU-2670, and SNU-2773). that Src inhibition may be an effective measure to overcome Elevated Src phosphorylation was detected in SNU2670HR trastuzumab resistance in HER2-positive cancer.",
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Resistance mechanism against trastuzumab in HER2-positive cancer cells and its negation by Src inhibition. / Jin, Mei Hua; Nam, Ah Rong; Park, Ji Eun; Bang, Ju Hee; Bang, Yung Jue; Oh, Do-Youn.

In: Molecular Cancer Therapeutics, Vol. 16, No. 6, 01.06.2017, p. 1145-1154.

Research output: Contribution to journalArticle

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AU - Nam, Ah Rong

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AU - Oh, Do-Youn

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