Mechanism of Honghua Oral Liquid in Alleviating Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg-1·d-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg-1·d-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Expert consensus on icotinib as adjuvant therapy for non-small cell lung cancer / 中华肿瘤杂志

Clinical studies have established the clinical application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant targeted therapy. Compared with chemotherapy, the high efficiency and low toxicity of targeted therapy increases the survival benefit of patients. Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.

Progress in epidermal growth factor receptor-tyrosine kinase inhibitors-associated interstitial lung disease / 中国胸心血管外科临床杂志

@#The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.

Clinical observation of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of EGFR-TKI acquired resistant advanced lung adenocarcinoma / 中国药房

OBJECTIVE To compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） acquired resistant advanced lung adenocarcinoma. METHODS The information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group （32 cases）， anlotinib combined chemotherapy group （24 cases） and bevacizumab combined chemotherapy group （28 cases）. Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection， and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy， patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally， once a day， for 14 consecutive days and 7 days of discontinuation， based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy， based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles， with one cycle every three weeks. The overall response rate （ORR）， disease control rate （DCR）， median progression-free survival （mPFS）， and the changes of serum tumor markers were compared among three groups before and after treatment； meanwhile， the occurrence of adverse drug reactions was recorded， and the 1-year survival rate was followed up. RESULTS After 4 treatment cycles， ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group （P＜0.05）； mPFS of the two groups were significantly longer than chemotherapy group， and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group （P＜0.05）. After 4 treatment cycles， the serum levels of tumor markers in three groups were significantly lower than before treatment， and both combined chemotherapy groups were significantly lower than chemotherapy group （P＜0.05）. There was no statistically significant difference in the incidence of adverse reactions such as nausea， vomiting， bone marrow suppression， and 1-year survival rate among the three groups of patients （P＞0.05）. CONCLUSIONS Bevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.

Small cell lung cancer: an overview of the targets

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

Diagnostic and prognostic value of ROR1 antigen in patients with chronic lymphocytic leukemia / 中华检验医学杂志

Objective:To detect the expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) antigen in chronic lymphocytic leukemia (CLL) and evaluate its diagnostic value and explore its correlation with the abnormalities of genetics and molecular biology.Methods:All of 209 newly diagnosed B-cell chronic lymphoproliferative disorders (B-CLPD) patients who were admitted to the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People′s Hospital) from November 2020 to November 2021 were collected retrospectively, including 70 cases of CLL with typical phenotype, 16 cases of CLL with atypical phenotype, 14 cases of MCL, and 109 cases of other types of B-CLPD. Multi-parameter flow cytometry (FCM) was used to detect the expression levels of ROR1 in tumor cells of 209 patients. And then the diagnostic value of ROR1 in CLL patients and its correlation with the genetic and molecular biological abnormalities were analyzed by c2 test and fourfold table assessment.Results:The positive expression rate of ROR1 in CLL patients was significantly higher than that in non-CLL patients (78%>11%, P<0.001); there was no significant difference of ROR1 expression between typical phenotype CLL and atypical phenotype CLL (81%>63%, P>0.05). The positive expression rate of ROR1 in atypical phenotype CLL was significantly higher than that in MCL (63%>21%, P<0.05). Additionally, there was significant difference in detection rate of chromosomal abnormalities between ROR1 +CLL group and ROR1 -CLL group. The detection rate of complex karyotype in ROR1 +CLL group was higher than that in ROR1 -CLL group (34%>14%, P<0.05). The CLL patients over 60 years old had higher ROR1 positive rate ( P<0.05). Conclusions:ROR1 can be helpful in the diagnosis of CLL, especially in the differential diagnosis of atypical phenotype CLL, MCL and other types of B-CLPD. Patients with ROR1 positive expression were older and more likely to detect complex chromosomal karyotypes.

A review: drug-drug interactions of epithelial growth factor receptor-tyrosine kinase inhibitors / 中华肿瘤杂志

Mutations in the epithelial growth factor receptor (EGFR) is a driving factor that causes non-small cell lung carcinoma (NSCLC). The epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a crucial discovery in the treatment of lung cancer, particularly the efficacy of EGFR-TKIs is superior to that of the standard chemotherapy for patients with EGFR mutation-positive advanced NSCLC. Patients with NSCLC use EGFR-TKIs and other medications simultaneously is commonly seen, especially among those with comorbidities, which increases the risk of drug-drug interactions (DDIs) of EGFR-TKIs. The most common mechanisms underlying the DDIs of EGFR-TKIs are modulations of cytochrome P450 (CYP) and drug transporters [including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)], as well as gastrointestinal acid-inhibitory drugs [proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RA)]. Inhibitors or inducers of CYP enzymes and drug transporters can inhibit or accelerate the metabolism of EGFR-TKIs, which increase or reduce the exposure of EGFR-TKIs, thereby affect the efficacy and safety of EGFR-TKIs. In addition, PPIs or H(2)RA can decrease the solubility, bioavailability and efficacy of EGFR-TKIs. This review summarizes the mechanisms of DDIs of gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib; the management recommendations for DDIs of those EGFR-TKIs from the Chinese and global guideline, as well as from the recent pre-clinical and clinical studies, which provide the reference and evidence for managing the combination therapies of EGFR-TKIs and other medications in clinics.

Study of neurotrophic factor receptor tyrosine kinase gene fusion in the precise treatment of wild-type gastrointestinal stromal tumor / 中华胃肠外科杂志

The neurotrophin receptor kinase (NTRK) gene encodes neurotrophic factor receptor tyrosine kinase (NTRK), which plays an important role in the development and function of the nervous system. NTRK gene fusion mutation results in the production of chimeric NTRK proteins, which have carcinogenic potential through constitutive activation or overexpression. NTRK gene fusion mutation can lead to a special type of wild type gastrointestinal stromal tumor (GIST), whose clinical manifestations and treatment are completely different from other types of GIST. This fusion mutation can be detected clinically by a variety of methods, including tumor DNA and RNA sequencing and immunohistochemical staining. In patients with NTRK fusion positive tumors, NTRK inhibitors such as larotrectinib and entrectinib have shown good antitumor efficacy, with clinical response rates as high as 75%. Therefore, there is a need to improve the recognition and detection of fuch patients and to improve their prognosis by individualized and precise treatment with TRK inhibitors.

The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) plus radiotherapy in the treatment of lung adenocarcinoma patients with central nervous system metastases: a meta-analysiss / 中国医师杂志

Objective:To systematically evaluate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combined with radiotherapy in the treatment of lung adenocarcinoma with central nervous system (CNS) metastasis.Methods:PubMed, EMBASE, Medline, Cochrane Library, clinical trials and other databases were searched to collect the clinical control studies of EGFR-TKI combined with radiotherapy versus EGFR-TKI or radiotherapy alone in the treatment of lung adenocarcinoma with CNS metastasis published at home and abroad from January 2012 to April 2019. After evaluating the data, Revman 5.3 software was used for meta-analysis.Results:10 studies involving 1 379 participants were included. The results indicated that compared with EGFR-TKI or radiotherapy alone, EGFR-TKI plus radiotherapy had a significant benefit on overall response rate (ORR) [ OR: 3.81, 95% CI(1.73, 8.39); P<0.01], overall survival (OS) [ HR: 0.60, 95% CI(0.41, 0.89); P=0.01], neurological progression free survival (nPFS) [ HR: 0.65, 95% CI(0.46, 0.91); P=0.01] compared with EGFR-TKI or radiotherapy alone. Conclusions:EGFR-TKI plus radiotherapy had better ORR, OS, nPFS compared with TKI or radiotherapy alone.

Comprehensive Treatment of An Advanced Lung Cancer Patient with EGFR Driver Gene Positive / 中国肺癌杂志

Lung cancer is the most common malignant tumor and the leading cause of cancer-related death worldwide. Most of the patients have distant metastasis when visiting the doctor, which seriously affects the survival time and quality of life of the patients. With the development of molecular targeted drugs, lung cancer treatment has been transformed from traditional chemotherapy to targeted therapy and precision medicine has been gradually applied in clinical practice, which can make lung cancer patients live longer and have a better quality of life. We present a case of advanced lung cancer patient who presented to Department of Thoracic Surgery of Beijing Haidian Hospital five years ago. We chose the reasonable treatment options though the genetic tests and circulating tumor DNA tests. We summarized the adverse reactions in the whole course of treatment. The comprehensive therapy we utilized, including targeted therapy, chemotherapy, antiangiogenic agents and local radiotherapy, have resulted in our patient with remaining alive. For advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutation positive, individualized treatment was conducted based on precise genotyping and dynamic monitoring, which can not only control the tumor, but also have mild toxic and side effects. The survival time of the patients was prolonged and the quality of life was guaranteed.
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Research Progress of Discoidin Domain Receptor 1 in Breast Cancer and Other Malignant Tumors / 中国医学科学院学报

Discoidin domain receptor 1(DDR1)is a critical member of the receptor tyrosine kinase family.It may be related to tumor invasion and metastasis,and the abnormal activation of DDR1 can lead to the occurrence and development of malignant tumors,inflammation,and fibrosis.DDR1 are involved in cell adhesion,migration,proliferation,secretion of cytokines,and remodeling of extracellular matrix,thus playing a critical role in various pathophysiological processes of the human body.In this review,we demonstrate the research progress of DDR1 in breast cancer and other malignant tumors,in order to provide a new theoretical basis for the prevention and treatment of breast cancer and other tumors.

Effect of almonertinib on the proliferation, invasion, and migration in non-small cell lung cancer cells / 中南大学学报(医学版)

OBJECTIVES@#Lung cancer is one of the most common malignant tumors in the world, and its lethality ranks the first among many malignant tumors. For non-small cell lung cancer (NSCLC) patients, due to the high mortality rate, the overall 5-year survival rate is less than 15%. When NSCLC undergoes local invasion, the 5-year survival rate is only 20%, and it is even lower when distant metastasis occurs up to 4%. Almonertinib is an innovative drug independently researched and developed by China with independent intellectual property rights. As an epidermal growth factor receptor tyrosine kinase inhibitor, almonertinib is mainly used for locally advanced or metastatic NSCLC patients with epidermal growth factor receptor (EGFR) T790M mutation. This study aims to investigate the effects of almonertinib on the proliferation, invasion and migration of NSCLC cells in vitro.@*METHODS@#NSCLC cells H1975 and PC-9 were cultured in vitro. The effects of almonertinib on the proliferation, apoptosis, invasion, and migration of H1975 and PC-9 cells were detected by CCK-8 assay, apoptotic assay and Transwell assay. The expression of invasion and migration related proteins was detected by Western blotting.@*RESULTS@#The CCK-8 experiment showed that almonertinib inhibited the proliferation of H1975 and PC-9 cells in a time- and dose-dependent manner. The IC@*CONCLUSIONS@#Almonertinib can inhibit the proliferation, invasion, and migration of NSCLCH1975 and PC-9 cells in vitro and vivo, and promote the apoptosis of H1975 and PC-9 cells. The underlying mechanism may be related to the inhibition of tumor cell epithelial mesenchymal transformation and metalloproteinase expression.

Role of metabolic reprogramming in drug resistance to epidermal growth factor tyrosine kinase inhibitors in non-small cell lung cancer / 中南大学学报(医学版)

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can effectively inhibit the growth of EGFR-dependent mutant non-small cell lung cancer (NSCLC). Unfortunately, NSCLC patients often develop severe drug resistance after long-term EGFR-TKI treatment. Studies have shown that the disorder of energy metabolism in tumor cells can induce EGFR-TKI resistance. Due to the drug action, gene mutation and other factors, tumor cells undergo metabolic reprogramming, which increases the metabolic rate and intensity of tumor cells, promotes the intake and synthesis of nutrients (such as sugar, fat and glutamine), forms a microenvironment conducive to tumor growth, enhances the bypass activation, phenotype transformation and abnormal proliferation of tumor cells, and inhibits the activity of immune cells and apoptosis of tumor cells, ultimately leading to drug resistance of tumor cells to EGFR-TKI. Therefore, targeting energy metabolism of NSCLC may be a potential way to alleviate TKI resistance.

Research Progress of New Generation EGFR-TKIs after Third-generation / 中国肺癌杂志

Lung cancer has the highest mortality rate in the world. The first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival time and quality of life of patients with non-small cell lung cancer (NSCLC) to some extent. However, after a period of progression-free survival, most patients develop drug resistance, in which T790M mutation is the mainly resistance mechanism. The third-generation EGFR-TKIs, represented by osimertinib, are found to have significant effect on this resistance. The effect is remarkable, but drug resistance is still inevitable. For example, C797S mutation, mesenchymal-epithelial transition (MET), RAS mutation, BRAF mutation, transformation of small cell lung cancer (SCLC), transformation of epithelial mesenchymal transition (EMT), etc. But, there is no standard and effective treatment after the third-generation EGFR-TKIs resistance. In this view, we summarize the research progress in the new generation EGFR-TKIs after third-generation, in order to provide some reference for the follow-up research and treatment.
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Advances in small molecule inhibitors of ACK1 / 药学学报

ACK1 (activated Cdc42-associated kinase) is a non-receptor tyrosine kinase, originally identified by its binding to the GTP-binding small GTPase Cdc42. It is widely expressed in human tissues and activated by various extracellular growth factors such as EGF, PDGF and TGF-β. The activated ACK1 mediates the signaling cascade by interacting with downstream effectors followed by their phosphorylation. In recent years, researchers have investigated the biological functions of ACK1 and its roles in cancer research. The gene amplification and overexpression of ACK1 is associated with a poor prognosis and metastasis in a variety of cancers including lung, ovarian and prostate cancers. Therefore, the development of small molecule inhibitors of ACK1 provides promising opportunities for cancer-targeted therapy. In this review, we briefly describe recent advances in understanding the activation and biological function of ACK1 and introduce its novel inhibitors with potential therapeutic activities in preclinical studies.

Pay Attention to Diagnosis and Treatment of Gastrointestinal Stromal Tumors / 胃肠病学

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. The receptor tyrosine kinase inhibitor imatinib mesylate is used for the standard treatment of GIST and has achieved remarkable results. Thus, GIST has become the most successful model for targeted therapy of solid tumors. GIST is quite different from other gastrointestinal tumors in pathological diagnosis, endoscopic and imaging diagnosis, surgical principles and drug treatment. Multidisciplinary collaborative model plays an important role in the diagnosis and treatment of GIST. Contemporary medicine has entered a new era of standardized, individualized and precise diagnosis and treatment at molecular level. Clinicians, especially those engaged in gastrointestinal tumors, should pay attention to and standardize the diagnosis and treatment of GIST, and apply the experience gained from GIST to the clinical practice of precision medicine.

Application of radiomics captured from CT to predict the EGFR mutation status and TKIs therapeutic sensitivity of advanced lung adenocarcinoma / 中华肿瘤杂志

Objective@#To explore the ability of computed-tomography (CT) radiomic features to predict the Epidermal growth factor receptor (EGFR) mutation status and the therapeutic response of advanced lung adenocarcinoma to EGFR- Tyrosine kinase inhibitors (TKIs) treatment.@*Methods@#A retrospective analysis was performed on 253 patients diagnosed as advanced lung adenocarcinoma, who underwent EGFR mutation detection, and those with EGFR sensitive mutation were treated with TKIs. Using the Lasso regression model and the 10 fold cross-validation method, the radiomic features of predicted EGFR mutation status and the screening of TKIs for sensitive populations were obtained. 715 radiomic features were extracted from unenhanced, arterial phase and venous phase, respectively.@*Results@#The area under curve (AUC) values of the multi-phases including unenhanced, arterial phase and venous phase of the EGFR mutation status validation group were 0.763, 0.807 and 0.808, respectively. The number of radiomic features extracted from the multi-phases were 5, 18 and 23, respectively, which could distinguish the EGFR mutation status. The AUC values of the multi-phases of the EGFR-TKIs sensitive validation group were 0.730, 0.833 and 0.895, respectively. The number of radiomic features extracted from the multi-phases were 3, 7 and 22, respectively, which can be used to screen the superior population for TKIs treatment. The efficiency of radiomic features extracted from venous phase in predicting EGFR mutant status and EGFR-TKIs sensitivity was significantly superior than those of unenhanced and arterial phase.@*Conclusions@#The radiomic features of CT scanning can be used as the radiomics biomarker to predict the EGFR mutation status of lung adenocarcinoma and to further screen the dominant population in TKIs therapy, which provides the basis for targeted therapy.

Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer / 中华肿瘤杂志

Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.

Efficacy of first generation EGFR-TKIs and chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations / 中华肿瘤杂志

Objective@#To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) compared with platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations.@*Methods@#Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (ⅢB/Ⅳ) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first-line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations.@*Results@#The objective response rates of patients with uncommon EGFR mutations receiving EGFR-TKIs or platinum-based chemotherapy were 33.0% and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression-free survival (PFS) of patients treated with EGFR-TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P=0.009). The overall survival of patients treated with EGFR-TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P=0.034). Multivariate analysis showed that distant metastases (P=0.001) and smoking history (P=0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations.@*Conclusions@#Compared with chemotherapy, the usage of first generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum-based chemotherapy shows a longer overall survival.

First-generation epithelial growth factor receptor tyrosine kinase inhibitor in the first-line treatment of advanced non-small cell lung cancer: 166 cases analysis of progression-free survival / 中国实用内科杂志

OBJECTIVE: Explore the clinical benefit factors of progression-free survival(PFS) in sensitive epithelial growth factor receptor(EGFR) gene mutated advanced non-small cell lung cancer patients treated with first-generation of EGFR tyrosine kinase inhibitor(TKI).METHODS: The clinical data of 166 patients who received first-line treatment with first-generation EGFR-TKI were retrospectively collected in 2016-2017 from Xiangya Hospital, Central South University. The patients were divided into three groups: PFS≤3 m,3 m