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PTEN deficiency as a predictive biomarker of resistance to HER2-targeted therapy in advanced gastric cancer

 Zhang X  ;  Park JS  ;  Park KH  ;  Kim KH  ;  Jung M  ;  Chung HC  ;  Rha SY  ;  Kim HS. 
 ONCOLOGY, Vol.88(2) : 76-85, 2015 
Journal Title
Issue Date
Adult ; Aged ; Biomarkers ; Class I Phosphatidylinositol 3-Kinases ; Drug Resistance, Neoplasm ; Female ; Humans ; Male ; Middle Aged ; Mutation ; PTEN Phosphohydrolase/analysis ; PTEN Phosphohydrolase/deficiency* ; Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/genetics ; Receptor, ErbB-2/antagonists & inhibitors* ; Stomach Neoplasms/chemistry ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/genetics ; Stomach Neoplasms/mortality
HER2 ; Gastric cancer ; PTEN ; PIK3CA ; Trastuzumab ; Lapatinib
BACKGROUND: To investigate the role of the phosphoinositide 3-kinase (PI3K) pathway activation in human epidermal growth factor receptor 2 (HER2)-targeted therapy.
METHODS: We evaluated the predictive roles of PI3K, catalytic alpha (PIK3CA), and phosphatase and tensin homolog (PTEN) in HER2-based therapy (either trastuzumab or lapatinib). PTEN expression and PIK3CA mutation were analyzed using immunohistochemistry and pyrosequencing.
RESULTS: Forty-eight patients received trastuzumab (n = 39) or lapatinib (n = 9) combination chemotherapy. PTEN loss was found in 47.9% (n = 23), but no PIK3CA mutations were identified. Twenty-six (54.1%) patients responded to HER2-based therapy, without a significant difference between patients with PTEN loss and those without (52.2 vs. 56.0%). Among the patients with responsive disease, time to best response did not differ by PTEN status, but the duration of response was significantly shorter for patients with PTEN loss (median 4.2 vs. 6.1 months, p = 0.04). In addition, patients with PTEN loss had a significantly shorter progression-free survival time (median 4.9 vs. 7.3 months, p = 0.047).
CONCLUSIONS: PTEN deficiency is an important predictive marker for early resistance to HER2 inhibitor treatment in gastric cancer patients. This finding may be useful for the development of drug combinations and identification of patients who need a modified treatment strategy.
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2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Ji Soo(박지수) ORCID logo https://orcid.org/0000-0002-0023-7740
Zhang, Xiang Lan(장향란)
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
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