KRAS mutation is one of the most frequent driver gene mutations found in patients with non-small cell lung cancer (NSCLC). KRAS-mutant NSCLC is highly heterogeneous. Various mutation types and different co-mutational signatures affect tumor biological behavior and therapeutic responses. NSCLC patients with KRAS mutations could relatively benefit from immunotherapy, while the effects of KRAS mutations on chemotherapy are still controversial. The treatment methods of KRAS-mutant lung cancer have followed the therapy of NSCLC without driver gene mutation for a long time. With the introduction of novel KRAS G12C inhibitors in the clinic, the therapeutic landscape has begun to change and has made the preliminary advance, and the combined therapies resulted in encouraging signals of efficacy both in preclinical and early phase trials. This paper reviews the biological and clinical characteristics as well as the latest treatment progress of KRAS-mutant NSCLC.

Seventy patients with advanced non-small-cell lung cancer (NSCLC) aged 65 or above were treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib or gefitinib from February 2006 to September 2010. The efficacy and toxicities of treatment were retrospectively analyzed.The overall response rate and disease control rate were 31.4％ and 84.3％,respectively. Themedian progression-free survival time and median survival time were 8.0 months and 13.5 months,respectively(P ＜ 0.05 ). One-year survival rate was 54.3％. Response rate ( CR + PR) ( 42.9％ ) anddisease control rate (94.3％ )in female patients were superior to males (20.0％ and 74.3％ ) (P ＜ 0.05 ).Non-smoking and PS score ＜ 2 were good predictors for survival.The side effects were generally mild and mainly were skin rash and diarrhea.

Non-small cell lung cancer (NSCLC) is a malignant tumor with rapid progress and high malignancy, accounting for 85% of all lung cancers. Treatment has shifted from traditional surgery, radiotherapy and chemotherapy to targeted therapy. Targeted therapy can prolong the survival of patients with positive driver gene fusion. With the continuous progress of biological research, targets related to NSCLC have gradually been discovered. Among the many driving genes of NSCLC, RET fusion is an important emerging target discovered in recent years. It has been confirmed to have a high incidence in non-smoking, young and low-differentiated NSCLC patients. This article reviews RET gene fusion in NSCLC, the relationship between the two and the treatment progress.

Background and objectiveIcotinib is the ifrst self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, geiftinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the effcacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients withEGFR mutation and wild-type.MethodsPatients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014.Re-sults hTe clinical data of 124 patients (99 withEGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. hTe patients’ overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; hTe patients withEGFR mutation, ORR was 63.6%, DCR was 93.9%. hTe ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment inEGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. hTe major adverse events were mild skin rash (30.6%) and diarrhea (16.1%).Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLCEGFR mutation patients.

Patients with operable non-small cell lung cancer (NSCLC) receiving neoadjuvant or adjuvant chemotherapy have a very limited improvement in 5-year survival rate. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have made a breakthrough in the treatment of EGFR-mutant advanced NSCLC, which shed light for the exploration of perioperative targeted therapy in NSCLC patients. Significant progress has been made in the research of targeted therapy of the first and third generation EGFR-TKI in perioperative patients. The availability of novel potent and less toxic targeted therapy has brought new treatments for the operable NSCLC. This article reviews the progress and existing problems of adjuvant and neoadjuvant targeted therapy in NSCLC harboring EGFR mutation.

Background and objective Status of epidermal growth factor receptor (EGFR) gene is a predictor of response to EGFR tyrosine kinase inhibitor (TKI). However, lile is know about the relationship between EGFR status and response to chemotherapy. We evaluated the prediction value of EGFR mutation status on response to first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods e data of 181 patients with stage IIIb/IV NSCLC who diagnosed by histopathology from January 10, 2006 to December 20, 2013 in Beijing Chest Hospital, Capital Medical University were collected. e relationships between EGFR gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed. Results All of the 181 patients’ EGFR statuses were determined. 75 (41.4%) patients har-bored EGFR-activating mutations and 106 (58.6%) patients were EGFR wild-type. All patients received first-line chemother-apy. e objective response rate (ORR) was 26.0% and disease control rate (DCR) was 70.2%. Patients with EGFR-activating mutations had a higher DCR than patients with EGFR wild-type (84.0% vs 60.4%, P=0.001) did. Subgroup analysis showed that the ORR and DCR in patients with EGFR exon 19 deletions were remarkably higher than those with EGFR wild-type (P= 0.049, 0.002, respectively). e DCR in patients with EGFR exon 21 L858R mutation was significantly higher than that in patients with EGFR wild-type (P=0.010). 168 patients were available for response evaluation in all of 181 patients and median PFS was 4.3 mo. e PFS of patients with adenocarcinoma was significantly higher than that patients with squamous cell carci-noma (4.7 mo vs 3.0 mo, P=0.036). e PFS in patients harbored EGFR-activating mutations was significantly higher than that in the patients with EGFR wild-type (6.3 mo vs 3.0 mo, P=0.002). e PFS of patients with a performance status (PS) of 0-1 was significantly higher than that in patients with a PS of 2 (4.4 months vs. 0.7 months, P= 0.016). Cox multivariate analysis indicates the EGFR-activating mutation is an independent factor aecting PFS (HR=0.654, 95%CI: 0.470-0.909, P=0.012). Conclusion EGFR-activating mutation is a predictor for PFS of first-line chemotherapy in advanced NSCLC patients.

Background and objective Activating mutations in epidermal growth factor receptor (EGFR) and KARS are important markers in non-small cell lung cancer. However, EGFR and KARS gene mutations in lung squamous cell carcinoma are rarely reported. hTe aim of this study was to analyze EGFR and KARS gene mutation rate and their relationship with clinical features in patients with lung squamous cell carcinomas. Methods A total of 139 patients undergoing treatment for na?ve lung squamous cell carcinomas with tumor tissue samples available for testing were recruited. EGFR and KARS mutation statuses of the tumor samples were detected using a mutant enriched liquid chip. Results Of the 139 cases of lung squamous cell carcinoma, EGFR mutations were detected in 25 cases (18%), KARS mutations were detected in 7 cases (5%), and the pres-ence of both EGFR and KARS mutations was detected in 1 case (0.7%). EGFR mutations occurred more otfen in females than in males (33.3%vs 16.5%) and in patients that never smoked than in those who smoke (29.6%vs 16.1%). However, the differ-ence did not reach statistical signiifcance (P>0.05). No signiifcant differences were observed in age, stage, and different biopsy type. KARS mutations occurred more otfen in males than in females (5.5%vs 0%), but the difference did not reach statistical signiifcance (P>0.05). No signiifcant differences were observed in age, stage, different biopsy type, and smoking status (P>0.05). Conclusion EGFR and KARS mutations were low in lung squamous cell carcinomas, and had no signiifcant correlation with clinical features. Before using tyrosine kinase inhibitor targeted therapy, EGFR and KARS mutations should be detected in pa-tients with lung squamous cell carcinomas.

Background and objectiveMutations in epidermal growth factor receptor (EGFR) andKARS are im-portant markers in non-small cell lung cancer, which are closely related to the clinical therapeutic effect. To analysis theEGFR andKARS gene mutation rate and its relationship with clinical features in patients with lung adenocarcinoma.Methods395 patients with treatment na?ve lung adenocarcinoma, tumor tissue samples were available for testing. Tumor sampleEGFR and KARS mutation status were detected using mutant enriched liquidchip.Results 395 cases of lung adenocarcinoma,EGFR mutations were detected in 192 cases (48.9%),KARS mutations were detected in 29 cases (7.8%), and the presence ofEGFR andKARS mutation were detected in 1 case (0.3%).EGFR mutations were found to occur signiifcantly more otfen in female than in male patients (62.0%vs 37.1%,P<0.001) and in never smokers than in smokers (61.9%vs 30.3%,P<0.001), no sig-niifcant differences were observed in age, stage and different biopsy type.KARS mutations were not found to have statistical signiifcance (P>0.05) in each clinical factors, only occurred in the wild typeEGFR gene in patients (13.5%, 27/200) was sig-niifcantly higher than that of patients withEGFR mutation (1.0%, 2/192), the difference was statistically signiifcant (P<0.001). ConclusionIn lung adenocarcinomas,EGFR mutation was higher in female and non-smoking patients,KARS mutation only in patients with wild-typeEGFR gene was higher. Before using TKI targeted therapy,EGFR andKARS mutations should be detected.

Background and objective Kirsten rat sarcoma viral oncogene (KARS) mutation is one of the major driver genes of non-small cell lung cancer (NSCLC). KARS is a resistant predictor of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), which raises controversy because of its role in chemotherapy sensitivity and prognosis. hTe aim of this study is to accumulate clinical experience in treating NSCLC patients harboringKARSmutation.MethodsA total of 107 NSCLC patients harboringKARSmutation were analyzed retrospectively. hTe effcacy was analyzed in terms of ifrst-line chemotherapy or EGFR-TKIs therapy.Results hTe objective response rate (ORR) to ifrst-line chemotherapy of 52 pa-tients with advanced disease harboringKARS mutation was 9.6%. hTe disease control rate (DCR) was 53.8%, and the median progression-free survival (PFS) was 3 months. hTe ORR to EGFR-TKIs therapy in 21 patients harboringKARS mutation and EGFR/KARS co-mutation was 9.5%; the DCR was 23.8%, and the median PFS was 1 month. hTe ORR and DCR to EGFR-TKIs therapy of patients withEGFR/KARS co-mutation were signiifcantly higher than those of patients withKARS mutation (50%vs 0,P=0.029; 75%vs 11.8%,P=0.043); the median PFS was also signiifcantly longer (3 monthsvs 1 month,P=0.004). Conclusion hTe effcacy to ifrst-line chemotherapy and EGFR-TKIs therapy in NSCLC patients harboringKARS mutation was poor; thus, new drugs should be developed. Furthermore, the existence ofEGFR/KARS co-mutation was conifrmed. Hence, EGFR-TKIs therapy should be administered to patients withEGFR/KARS co-mutation.

Immune checkpoint inhibitor (ICI) has been proven to be a major breakthrough in the treatment of various tumor types. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Myasthenia gravis (MG) is one of rare but life-threatening irAEs, with acute onset and rapid progression after ICI initiation. Early diagnosis and active treatment are crucial. Herein, we review recent literatures to provide guidance to frequently asked questions concerning the diagnosis and management of ICI-MG.