Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2018; 9:35285.

EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment

Hongjuan Zhang, Cheng Zhan, Ji Ke, Zhiqiang Xue, Aiqun Zhang, Kaifeng Xu, Zhirong Shen, Lei Yu and Liang Chen _

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Oncotarget. 2016; 7:3367-3378. https://doi.org/10.18632/oncotarget.6491

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Abstract

Hongjuan Zhang1,2, Cheng Zhan2, Ji Ke3, Zhiqiang Xue4, Aiqun Zhang4, Kaifeng Xu5, Zhirong Shen2,6, Lei Yu3, Liang Chen2,7

1School of Life Science, Tsinghua University, Beijing 100084, China

2National Institute of Biological Sciences, Beijing 102206, China

3Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

4The General Hospital of People’s Liberation Army (301 Hospital), Beijing 100853, China

5Peking Union Medical College Hospital, Beijing 100730, China

6Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China

7National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, 102206, China

Correspondence to:

Liang Chen, e-mail: chenliang@nibs.ac.cn

Zhirong Shen, e-mail: shenzhirong@nibs.ac.cn

Lei Yu, e-mail: yulei1118@sohu.com

Keywords: EGFR, hyperthermic chemotherapy, lung cancer, kinase domain mutation

Received: June 15, 2015     Accepted: November 16, 2015     Published: December 08, 2015

ABSTRACT

Lung cancer is the global leading cause of cancer-related deaths. A significant portion of lung cancer patients harbor kinase domain mutations in the epidermal growth factor receptor (EGFR). While EGFR tyrosine kinase inhibitors (TKI) effectively shrink tumors harboring mutant EGFR, clinical efficacy is limited by the development of TKI resistance. Effective alternatives are desperately needed in clinic for treating EGFR kinase domain mutation positive lung cancer. In our clinic in treating M1a lung cancer patients through intrapleural perfusion with hyperthermic chemotherapy (IPHC) followed by cycles of systemic chemotherapy (we termed this procedure IPHC complete treatment, IPHC-CT), we found dramatic tumor shrinkage in mutant EGFR-positive patients. We further confirmed the sensitivity of EGFR mutation-positive lung cancer cell lines derived from patients to HC (hyperthermic chemotherapy) treatment. We found that hyperthermia promoted accumulation of cisplatin in lung cancer cells. Hyperthermia and cisplatin synergistically downregulated the EGFR protein level, leading to quenching of signal from EGFR and induction of apoptosis. Our work therefore showed IPHC-CT is an effective treatment for EGFR kinase domain mutation positive lung cancer patients.


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