[Estimation of venous thromboembolism risk with thrombotic biomarkers in cancer patients].

OBJECTIVE: To assess the value of thrombotic biomarkers in estimation of venous thromboembolism (VTE) risk in cancer patients. METHODS: A total of 1473 cancer patients treated in the Tianjin Medical University General Hospital from 2009 to 201 were selected, including 845 males and 628 females in the age of 56 ± 17 years. The activities of von Willebrand factor antigen (vWF:Ag), factor VII (F VII:A), factor VIII (F VIII:A), antithrombin (AT:A), protein C (PC:A) and protein S (PS:A) were assayed using an ACL TOP 700 blood coagulation analyzer. The level of D-dimer (D-D) was assayed using the Biomerieux Mini Vidas Automated Immunoassay Analyzer. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic performance of the parameters. Cox regression analysis model was applied to evaluate the effect on prognosis, and Kaplan-Meier curve was used to implement the survival analysis. RESULTS: The levels of vWF:Ag, D-D, and F VIII:A were significantly higher in all the specified tumor groups ( except the other tumor group ) than that of the control groups (P < 0.05). F VIII:A was significantly higher than that in the control group in all tumor groups except the renal carcinoma, prostatic cancer, lymphoma groups and the other tumor group (P < 0.05). The PC:A level was significantly lower in all tumor patients groups than in the control group, except glioma, breast cancer, gastric carcinoma, renal carcinoma and the other tumors groups (P < 0.05). The PS: A level was significantly lower in all tumor groups than in the control group, except the glioma, breast cancer, prostatic cancer, lymphoma and the other tumors groups (P<0.05). The AT: A level was significantly lower in all tumor groups than in the control group (P<0.05). When the optimum cut-off point of vWF:Ag for VTE diagnosis was 192% in the cancer group, the area under ROC curve = 0.828 (95% CI: 0.716 to 0.939). When the optimum cut-off point of D-dimer for VTE diagnosis was 1484 ng/ml in the cancer group, the area under ROC curve = 0.915 (95% confidence interval: 0. 840 to 0.988). When the optimum cut-off point of PC: A for VTE diagnosis was 75.2% in the cancer group, the area under ROC curve = 0.764 (95% confidence interval: 0.630 to 0.898). The Cox analysis showed that age, surgery, chemotherapy and D-dimer were independent risk factors for VTE event within three months in cancer patients. The cumulative probability of VTE was increased significantly in the cancer patients if whose plasma D-dimer level was over the cut-off value. CONCLUSIONS: The plasma D-dimer level is obviously increased in cancer patients, and there is a relevance to thrombosis risk stratification and VTE cumulative probability. It is with good diagnostic performance, and may be used as an effective marker in estimation of VTE risk within 3 months in cancer patients.

Frst-line treatment of Zorifertinib in EGFR-mutant NSCLC with CNS metastases:a report of two cases / 天津医药

Objective To investigate the efficacy of Zorifertinib in first-line treatment of patients with untreated epidermal growth factor receptor(EGFR)mutation in non-small-cell lung cancer(NSCLC)with central nervous system(CNS)metastases.Methods Two patients received Zorifertinib as first-line treatment.The response of tumor treatment was evaluated by response evaluation criteria in solid tumors version 1.1(RECEST v1.1)and RANO criteria for brain metastases(RANO-BM).Results Case 1 had EGFR exon 19del mutation and multiple brain metastases at baseline.After 51.4 months of treatment with Zorifertinib,case 1 still maintained partial response(PR)in lung lesions and complete response(CR)in intracranial lesions.Case 2 had EGFR exon 19del mutation and a single brain metastasis at baseline.Case 2 achieved PR in lung lesions and CR in intracranial lesions during the treatment with Zorifertinib.After 13.7 months,lung disease progression(PD)and new single brain metastases occurred.The comprehensive evaluation was PD.Case 1 had three-grade treatment-related adverse events(TRAEs),including dry skin,and other TRAEs were rash,abnormal liver function and diarrhea.The TRAEs were generally controllable.Conclusion Zorifertinib has a good effect on controlling intracranial and extracranial lesions in patients with EGFR-mutated NSCLC with CNS metastases.The efficacy of Zorifertinib is consistent with the EVEREST study.Zorifertinib can be one of the first-line initial treatment options.

Research Progress of BRAF Fusion in Non-small Cell Lung Cancer / 中国肺癌杂志

In advanced non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation is highly malignant and has poor prognosis, and currently Dabrafenib in combination with Trametinib is approved for first-line treatment of patients with BRAF V600 mutation. In addition to mutations, BRAF fusion can also occur. With the development of gene detection, the detection of BRAF fusion is gradually increasing, but there is a lack of effective therapeutic strategies for BRAF fusion. In this paper, we review the clinical characteristics, mechanism of action, and clinical treatment of BRAF fusion to provide a basis for the treatment of BRAF fusion in NSCLC patients.
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Initial Treatment of Aumolertinib in Combination with Bevacizumab for Advanced NSCLC with Primary EGFR T790M Mutation: A Report of Three Cases and Literature Review / 中国肺癌杂志

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
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Research Progress of Klotho in Lung Neoplasms / 中国肺癌杂志

Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.
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DNA Damage Repair System and Antineoplastic Agents in Lung Cancer / 中国肺癌杂志

DNA damage repair (DDR) system plays an important role in maintaining of genomic stability. Accumulation of DNA lesions or deficiency of DDR system could drive tumorigenesis as well as promote tumor progression; meanwhile, they could also provide therapeutic opportunities and targets. Of all the antineoplastic agents of lung cancers, many of them targeted or were associated with DNA damage and repair pathways, such as chemotherapies and antibody-drug conjugates which were designed directly causing DNA damages, targeted drugs inhibiting DNA repair pathways, and immune-checkpoint inhibitors. In this review, we described the role of DNA damage and repair pathways in antitumor activity of the above agents, as well as summarized the application and clinical investigations of these antineoplastic agents in lung cancers, in order to provide more information for exploring precision and effective strategies for the treatment of lung cancer based on the mechanism of DNA damage and repair.
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Immune Checkpoint Inhibitors Related Diabetes Mellitus: A Report of 2 Cases and Literature Review / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) are widely used in clinic, and the incidence of rare adverse events are increasing. The aim of this paper is to better define the rare adverse effect of diabetes mellitus associated with ICIs. We report 2 cases of diabetes mellitus associated with ICIs. Literature review was conducted and we discussed the clinical presentation, potential mechanisms and suggestions for optimal management. Two patients were both elderly women, case 1 had increased blood glucose after 7 months of using Durvalumab, and cases 2 had diabetic ketoacidosis after 6 weeks of using Pembrolizumab. Both patients were administered exogenous insulin to control blood glucose. Case 1 has been treated with Durvalumab until now and case 2 discontinued using of Pembrolizumab. HLA genotypes and other factors may explain the risk factors of diabetes associated with ICIs in some individuals. Diabetes mellitus associated with ICIs is an uncommon but potentially life-threatening endocrine system adverse event, which requires doctors to be vigilant. The patients who use ICIs need to monitor blood glucose. If they have hyperglycemia, endocrinologists should be asked to assist in diagnosis and treatment.
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Two Case Reports of Type 2 Diabetes Induced by Immune Checkpoint Inhibitors Combined with Chemotherapy / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) have become an important means of cancer treatment, and their application in the clinic is becoming more and more widespread. The adverse reactions caused by ICIs are gradually recognized. Among them, immunotherapy-related diabetes is a rare adverse reaction and type 1 diabetes mellitusis common. With the wide application of ICIs combined with chemotherapy in lung cancer patients, patients with type 2 diabetes mellitus have gradually been discovered during the treatment. However, the effect of continued use of ICIs maintenance therapy on blood glucose and ICIs treatment process in these patients is still unclear. This article reports two cases of type 2 diabetes mellitus induced by immune checkpoint inhibitor combined with chemotherapy, one of whom converted to type 1 diabetes mellitus, in order to increase the understanding of immunotherapy-related diabetes.
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Gene Fusions as Acquired Resistance Mechanisms of EGFR-TKI / 中国肺癌杂志

Patients with sensitive epidermal growth factor receptor (EGFR) mutations often respond to tyrosine kinase inhibitors (TKIs), but acquired resistance will eventually develop. The most common mechanisms of acquired resistance include secondary EGFR mutation, MET amplification, and histologic transformation. Besides, gene fusions could also mediate the process of acquired resistance. Various gene fusions including rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and anaplastic lymphoma kinase (ALK) could take place after TKIs resistance, the incidence of which is around 1%. The clinical cases and experiments both in vitro and in vivo have proved the role of gene fusions in EGFR-TKI resistance. The combination of EGFR inhibitors and gene fusion inhibitors might be an effective therapeutic method. The understanding of gene fusions at EGFR-TKI resistance may contribute to the subsequent diagnosis and treatment strategy.

Research Progress of Targeted Therapy for HER2 Gene in Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the most common malignancy tumor. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer. Human epidermal growth factor receptor-2 (HER2) is a tyrosine kinase receptor in ERBB/HER family, which activates downstream signal transduction with other family members such as epidermal growth factor receptor (EGFR). HER2 gene mutation is closely related to the progression of many epithelial cell cancers. Tumors with high expression of HER2 show strong metastasis and invasion ability, poor sensitivity to chemotherapy, and are prone to relapse. At present, lung cancer driven gene targeted therapy has made rapid progress. Although the frequency of HER2 gene mutation in NSCLC is lower than that of EGFR, its driving mechanism in lung cancer is clear and partial targeted therapy is effective, which may become a new standard treatment in the future. This review focuses on the research progress of HER2 gene mutation in the treatment of NSCLC.
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Research Progress of Immune Checkpoint Inhibitor Therapy for BRAF Mutation in Non-small Cell Lung Cancer / 中国肺癌杂志

BRAF gene mutation is found in about 2%-4% of the patients with non-small cell lung cancer (NSCLC). This type of NSCLC is characterized by high malignancy, low efficacy of chemotherapy and poor prognosis. Although the combination treatment of BRAF inhibitor and MEK inhibitor has achieved remarkable results in advanced NSCLC patients with BRAF V600E mutation, which has been written into the National Comprehensive Cancer Network (NCCN) guidelines, severe side effects of the combination therapy are frequently observed. There isn't effective treatment strategy after drug resistance, and targeted therapy for non-V600E mutation patients is still lacking. In this paper, we summarized the researches on expression of immune markers in NSCLC patients with mutant BRAF and analyzed the studies on efficacy of immune checkpoint inhibitor (ICI), so as to provide more options for prolonging survival of the patients.
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Immunotherapy in Epidermal Growth Factor Receptor-mutant Non-small Cell Lung Cancer / 中国肺癌杂志

Targeted therapy and immunotherapy are important treatments for non-small cell lung cancer (NSCLC). At present, the clinical and basic research of epidermal growth factor receptor (EGFR) mutation NSCLC is still in the exploratory stage, needing to optimize the efficacy, combination, sequence and dosage of immunotherapy and other treatments, to clarify the relationship between EGFR mutation, immune microenvironment and the efficacy of immunotherapy. In this review, we summarized the newly updated data about immunotherapy in EGFR mutant NSCLC in term of pre-clinical study, programmed cell death protein ligand 1 (PD-L1) expression, tumor mutation burden and treatment.
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Advanced Research on Non-small Cell Lung Cancer with De Novo T790M Mutation / 中国肺癌杂志

With the development of sequencing technology, the detection rate of de novo T790M mutation is increasing. The emergence of the third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide treatment opportunities. Secondary T790M mutation is often emphasized in clinic, but de novo T790M mutation is neglected. This review found that the incidence of de novo T790M mutation fluctuated greatly, which was mainly affected by sequencing techniques. The de novo T790M mutation is mainly low in mutation abundance, easy to combine with other gene changes, a poor predictor and prognostic factor and the efficacy of the first and second generation EGFR-TKIs is limited. The therapeutic value of osimertinib needs to be studied.
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Prognostic value and initial exploratory research on TNM staging method of tumor deposits in stage III colon cancer / 中华胃肠外科杂志

Objective@#To investigate the effect of tumor deposits (TD) on the prognosis of patients with stage III colon cancer, and to explore whether TD number included into regional lymph node count can predict the prognosis more accurately.@*Methods@#A retrospective cohort study was carried out. Case inclusion criteria: (1) primary colon cancer; (2) undergoing colon cancer radical operation; (3) definite pathological diagnosis; (4) colon cancer stage III according to AJCC 8th edition; (5) complete follow-up data; (6) without preoperative neoadjuvant treatment. Clinicopathological data of 296 patients undergoing colon cancer radical operation from January 2005 to December 2008 in the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively collected. The effect of TD and its amount on the prognosis was evaluated. Colon cancer TNM staging method based on the 8th edition of AJCC was compared with the modified TNM staging (mTNM) adjusted by the number of TD. The differences of the disease-free survival (DFS) and overall survival (OS) between groups were also examined. The Kaplan-Meier curve was used to analyze the survival, and prognostic factors were analyzed by Cox univariate and multivariate analyses.@*Results@#Among 296 patients with stage III colon cancer, 78 patients had TD. The median number of TD was 2 (1-10). Tumor T stage, N stage, vascular tumor thrombus and preoperative carcinoembryonic antigen (CEA) were associated with TD in patients with colon cancer (all P<0.05). The right hemicolon appears likely to have TD than left hemicolon, but the difference was not statistically significant (P=0.059). The median follow-up of the whole group was 71 (6-102) months. During the follow-up period, 129 patients (43.6%) had recurrence or metastasis, and 111 patients died (37.5%). The 5-year DFS in TD group was 44.9%, which was lower than that in the non-TD group (60.6%), with statistically significant difference (P=0.003). The 5-year OS in TD group was 50.0%, which was also lower than 67.0% in the non-TD group, and the difference was statistically significant (P=0.002). According to TD number, patients were divided into 3 groups: 1 TD (25 cases), 2-3 TD (32 cases), ≥4 TD (21 cases). The 5-year DFS in these 3 groups was 68%, 56.3%, and 0, respectively (P<0.001), and 5-year OS was 76%, 59.4%, and 4.8% respectively (P<0.001). Univariate analysis showed that TD presence (95% CI: 1.234-2.694, P=0.003) and TD number (95% CI: 3.531-14.138, P<0.001) were associated with the prognosis of patients with stage III colon cancer. At the same time, age, tumor N stage, tumor location, chemotherapy, and preoperative CEA elevation were also associated with the prognosis of stage III colon cancer patients (all P<0.05). Multivariate analysis revealed that TD presence (HR=1.957, 95%CI: 1.269-3.017, P=0.002) and TD number (HR=8.020, 95% CI: 3.414-18.842, P<0.001) were still independent risk factors for the prognosis of patients with stage III colon cancer.According to the TD number counted as metastatic lymph nodes, in 78 patients with TD, 24 patients were upstaged in N stage, and 16 patients upstaged from TNM stage IIIB to stage IIIC. For 16 stage IIIB cases with staging modification, 30 unadjusted stage IIIB cases with TD, and 148 stage IIIB cases without TD, the 5-year OS was 37.5%, 73.3% and 76.4%, respectively with significant difference (P<0.001). However, for 16 patients adjusted as stage IIIC (mTNM), 32 patients with unchanged stage IIIC with TD (TNM, AJCC 8th edition), and 63 stage IIIC cases without TD, the 5-year OS was 37.5%, 36.4%, and 41.3%, respectively without significant difference (P=0.707).@*Conclusions@#TD presence and TD number are independent risk factors for prognosis of stage III colon cancerpatients. TNM staging evaluation with lymph node number including TD number can predict the prognosis of patients more accurately.

Molecular Mechanism and Progression of Primary Resistance to EGFR-TKI - Analysis of 2 Cases / 中国肺癌杂志

Tyrosine kinase inhibitor (TKI) have been proved to be effective in the treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) sensitive mutation, which is superior to chemotherapy. However, there are still some patients with sensitive mutations have primary drug resistance. It may be related to the coexistence of susceptible and resistant mutations of EGFR gene, downstream mutations of EGFR pathway, MET amplification and BIM deletion polymorphism. We present 2 cases of primary drug resistance and analyze the reasons.
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Clinical efficacy and safety of the anti-fungus treatment in advanced elderly patients with fungemia admitted into geriatric ICU / 中华老年医学杂志

Objective To observe the species distribution,clinical features,efficacy and safety of anti-fungus therapy in advanced elderly patients with fungemia.Methods Clinical data of patients aged 70 years and over with fungemia admitted into geriatric intensive care unit (GICU) of our hospital from Nov.2012 to Nov.2017 were retrospectively analyzed.The specie distribution,liver toxicity,differences in biochemical liver and renal functions before and after 28 days of treatment between the easpofungin group and the azole group (fluconazole plus voriconazole),and 28-d survival rate and its risk factors for death were analyzed.Results A total of 72 patients were enrolled,with a median age of 85.5 years (83,90),a median score of Acute Physiology and Chronic Health Enquiry (APACHE-Ⅱ) of 25.5 (20.3,31.5),a median score of Sequential Organ Failure Assessment (SOFA) 7 (4.0,9.8).There were 33 patients (45.8％) with diabetes,2 patients (2.8％) with hematological diseases,44 patients (61.1％) with solid tumors and 18 patients (25.0％) with renal insufficiency.Thirty patients (41.7％) needed mechanical ventilation.The detection rate of Candida para psilosis was 73.6％ (53 cases),Candida famata 9.7％ (7 cases),Candida tropicalis 5.6％ (4 cases),Candida albicans 2.8％ (2 cases),Candida glabrata 2.8％ (2 cases) and others 5.6％ (4 cases).The incidence rate of total liver toxicity was 23.6％ after anti-fungus treatment.After 28 days of treatment,29 patients survived in the caspofungin group (n=42) and 16 patients survived in the azole group (n=30).There were no significant differences in liver and renal function between the two groups before and after treatment.Logistic regression analysis showed that solid tumors (OR:19.904,95％CI:1.944-203.808) and the median APACHE Ⅱ score were the independent risk factors for 28-day death in advanced patients with fungemia.Conclusions Fungemia is becoming more and more prominent in the GICU,which requires clinician's constant attention in order to provide more basis for the treatment of fungemia in elderly patients.

Clinical efficacy and safety of the anti-fungus treatment in advanced elderly patients with fungemia admitted into geriatric ICU / 中华老年医学杂志

Objective@#To observe the species distribution, clinical features, efficacy and safety of anti-fungus therapy in advanced elderly patients with fungemia.@*Methods@#Clinical data of patients aged 70 years and over with fungemia admitted into geriatric intensive care unit (GICU) of our hospital from Nov. 2012 to Nov. 2017 were retrospectively analyzed. The specie distribution, liver toxicity, differences in biochemical liver and renal functions before and after 28 days of treatment between the caspofungin group and the azole group (fluconazole plus voriconazole), and 28-d survival rate and its risk factors for death were analyzed.@*Results@#A total of 72 patients were enrolled, with a median age of 85.5 years (83, 90), a median score of Acute Physiology and Chronic Health Enquiry (APACHE-Ⅱ) of 25.5 (20.3, 31.5), a median score of Sequential Organ Failure Assessment (SOFA) 7 (4.0, 9.8). There were 33 patients (45.8%) with diabetes, 2 patients (2.8%) with hematological diseases, 44 patients (61.1%) with solid tumors and 18 patients (25.0%) with renal insufficiency. Thirty patients (41.7%) needed mechanical ventilation. The detection rate of Candida parapsilosis was 73.6% (53 cases), Candida famata 9.7% (7 cases), Candida tropicalis 5.6% (4 cases), Candida albicans 2.8% (2 cases), Candida glabrata 2.8% (2 cases) and others 5.6% (4 cases). The incidence rate of total liver toxicity was 23.6% after anti-fungus treatment. After 28 days of treatment, 29 patients survived in the caspofungin group (n=42) and 16 patients survived in the azole group (n=30). There were no significant differences in liver and renal function between the two groups before and after treatment. Logistic regression analysis showed that solid tumors (OR: 19.904, 95%CI: 1.944-203.808) and the median APACHE Ⅱ score were the independent risk factors for 28-day death in advanced patients with fungemia.@*Conclusions@#Fungemia is becoming more and more prominent in the GICU, which requires clinician’s constant attention in order to provide more basis for the treatment of fungemia in elderly patients.

Clinical Development of Immunotherapy for Small Cell Lung Cancer / 中国肺癌杂志

Small cell lung cancer (SCLC), which accounts for about 15% of lung cancer cases, is an aggressive disease characterized by rapid growth and early widespread metastasis. Despite sensitive to chemotherapy and radiotherapy, SCLC is vulnerable to get resistant and has high recurrence rates. In recent years, immunotherapy has shown good antitumor activity, especially programmed death receptor-1/ligand-L1 (PD-1/L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) Checkpoint inhibitors have changed the pattern of tumor treatment, and SCLC has high immunogenicity, high mutation load and other favorable immune factors, so immuno-checkpoint inhibitors may become an important breakthrough in SCLC treatment. This article will briefly review the clinical research of immunotherapy for small cell lung cancer.
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Advances in Double Mutations of EGFR and ALK Gene in Non-small Cell Lung Cancer / 中国肺癌杂志

Molecular target therapy is one of the most popular field of non-small cell lung cancer (NSCLC) treatmnet. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearragement are the most important two oncogenic drivers in NSCLC, early studies suggested that EGFR mutations and ALK rearrangements are mutually exclusive, but isolated cases or small sample research with concomitant EGFR and ALK alterations have been constantly reported. The co-occurrence of EGFR mutations and anaplastic lymphoma kinase (ALK) rearrangements constitutes a rare molecular, the frequency of EGFR/ALK co-alterations was about 1%, however, little has been known about clinicopathologic feature and treatment. This review summarized published case report, EGFR and ALK alterations are common in female, Asian origin, never smoker, IV stage, and denocarcinomas. First-line treatment can choose EGFR or ALK tyrosine kinase inhibitors (TKIs). However, studies about the origin and resistance mechanism in EGFR/ALK co-alterations are little, require more experimental and clinical research.
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Research Progress of Targeted Therapy for BRAF Mutation in Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Targeted therapy is one of the major treatment modalities in advanced non-small cell lung cancer (NSCLC) with sensitive driver gene mutations. BRAF is considered a promising oncogenic driver in NSCLC after the discovery of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion and ROS1 rearrangement. BRAF V600E mutation accounts for more than half of BRAF mutations, which is a potential therapeutic target for advanced NSCLC. This review aims to summarize the advancements of BRAF gene mutation and targeted therapy for BRAF mutation in NSCLC.
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