Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a relative rare but highly aggressive neoplasm which is associated with asbestos exposure in most patients. The majority of patients are diagnosed in advanced stages so patients neither benefit from chemotherapy (e.g. pemetrexed-platinum combination) nor from surgery. It has been reported that cellular-mesenchymal to epithelial transition factor (MET) and epidermal growth factor receptor (EGFR) were critical for MPM cell proliferation. Moreover, targeting MET and EGFR drugs have gained promising results on anti-tumor therapy. Here, a striking difference in overall survival was observed between the MET and EGFR co-expression group (median survival time = 13.5 months) and non-co-expression group (median survival time = 20.5 months). In addition, treatment with combination of crizotinib and afatinib showed stronger inhibition on cell proliferation of MPM than the treatment by either one in vitro and in vivo. In conclusion, our data illustrated that crizotinib combined with afatinib may be a potentially effective strategy for treating MPM patients with over-expression of MET and EGFR.
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterGuangzhou 510060, China; Guangdong Esophageal Cancer InstituteGuangzhou 510060, China.
Liyan
L
Huang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Muyan
M
Cai
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Xu
X
Zhang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterGuangzhou 510060, China; Guangdong Esophageal Cancer InstituteGuangzhou 510060, China.
Fang
F
Wang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Likun
L
Chen
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Meng
M
Xu
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Ke
K
Yang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterGuangzhou 510060, China; Guangdong Esophageal Cancer InstituteGuangzhou 510060, China.
Zhen
Z
Chen
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center Guangzhou 510060, China.
Xiaokun
X
Wang
Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer CenterGuangzhou 510060, China; Guangdong Esophageal Cancer InstituteGuangzhou 510060, China.
Liwu
L
Fu
EGFR; MET; Malignant pleural mesothelioma; afatinib; crizotinib