Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance

Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.

Application of Serum HE4 in the Diagnosis of Lung Cancer / 现代检验医学杂志

Objective To investigate the diagnostic values of human epididymis (HE4)in lung cancer.Methods 80 patients with lung cancer were the experimental group,30 patients with benign pulmonary disease were the benign control group,and 30 healthy people were healthy control group.The levels of carcinoma embryonic antigen (CEA),cytokeratin protein fragment 21-1 (CYFRA21-1),neuron specific enolase (NSE) and HE4 in serum were detected.Results The levels of CEA,NSE,CYFRA21-1 and HE4 in lung cancer patients were higher than those in both the benign control group and the healthy control group (P＜0.05).The areas (AUC) under the receiver operating characteristic (ROC curve) were 0.870,0.818,0.746 and 0.897 for serum CEA,NSE,CYFRA21-1 and HE4 levels in diagnosis of lung cancer.The levels of CEA and HE4 were higher in patients with adenocarcinoma,the level of CYFRA21-1 was higher in patients with squamous cell carcinoma,the level of NSE was higher in patients with small cell lung cancer (SCLC) (P＜0.05).The detections of CYFRA21-1 (AUC=1.000),CEA (AUC=0.727) and HE4 (AUC=0.622) in serum are favorable for the diagnosis of squamous cell carcinoma,The detections of serum CEA (AUC=0.954) and HE4 (AUC=0.944) levels are favorable for the diagnosis of adenocarcinoma,and the detections of NSE (AUC=0.876) was favorable for the diagnosis of SCLC (P＜0.05).Conclusion The levels of CEA,NSE,CYFRA21-1 and HE4 in serum were abnormal in patients with lung cancer.The HE4 level in the patients was correlated with the pathological types and the metastasis of lung cancer.The detection of serum HE4 could be used in the diagnosis and evaluation of lung cancer.

LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor

Lung cancer is featured with high mortality, with a 15% five-year survival rate worldwide. Genetic alterations, such as loss of function of tumor suppressor genes, frequently contribute to lung cancer initiation, progression and metastasis. Liver kinase B1 (LKB1), as a serine/threonine kinase and tumor suppressor, is frequently mutated and inactivated in non-small cell lung cancer (NSCLC). Recent studies have provided strong evidences that LKB1 loss promotes lung cancerigenesis process, especially lung cancer progression and metastasis. This review will summarize recent progress on how LKB1 modulates the process of lung cancerigenesis, emphasizing on LKB1 downstream signaling pathways and biological functions. We will further discuss the potential development of prognostic biomarkers or therapeutic targets in lung cancer clinic based on the molecular alteration associated with deregulated LKB1 signaling.