title: EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment.
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.
authors.affiliation: School of Life Science, Tsinghua University, Beijing 100084, China.|National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Ke
authors.affiliation: The General Hospital of People's Liberation Army (301 Hospital), Beijing 100853, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Xue
authors.affiliation: The General Hospital of People's Liberation Army (301 Hospital), Beijing 100853, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.|Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.|National Institute of Biological Sciences, Collaborative Innovation Center for Cancer Medicine, Beijing, 102206, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010477:Perfusion; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; hyperthermic chemotherapy; kinase domain mutation; lung cancer