Currently targeted therapy of breast cancer therapy has become the hot research field and a kind of brand-new biological treatment mode after three traditional pattern of the surgery, radiotherapy and chemotherapy for breast cancer. Molecular targeted therapy is aimed at the target that may cause cancer cells, such as protocarcinogenic genes and tumor-suppressor genes, cell signaling pathways, cytokines and receptors, antiangiogenesis etc. It can reverse malignant biology behavior to inhibit tumor cell growth from the molecular level and has the advantages of high specific effects and low side effects. This paper focuses on the drug of the molecular targeted therapy for breast cancer and the latest progress of targeted therapy.

Objective To investigate the combined effect of exemestane and low-dose methotrexate on exemestane-resistant MCF-7 human breast cancer cells( MCF-7/EXE). Methods Antiproliferative effects of exemestane and low-dose of methotrexate, alone and in combination on growth of MCF-7/EXE cells were assessed by using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro by using the combination index ( CI) method. The cell cycle distribution was analyzed by flow cytometry in a half inhibitory concentration of exemestane and low-dose of methotrexate . The changes of apoptosis on MCF-7/EXE cells exposed to two drugs alone or in com-bination were observed by fluorescence microscope. The expression of Bcl-2,AKT,P-AKT and cyclooxygenase-2 was investigated by Western blot. Results MTT assays indicated that the combination treatment apparently decreased the viability of MCF-7/EXE cells compared to single drug treatment (CI<0. 9). In addition, the combination of exemestane and low-dose methotrexate exhibited a synergistic inhibition of cell proliferation, arrested the cell cycle in the S phase significantly and produced a stronger inhibitory effects on P-AKT, Bcl-2 and cyclooxygenase-2 ex-pression than control or individual drug treatment. Conclusion The combination of the two inhibitors significantly increases the response as compared to single agent treatment, suggesting that combination treatment which can re-verse the resistance of exemestane could be a more effective approach to breast cancer.

Objective To explore miR-21 regulation of Smad7 in lung cancer A549 cell line as well as its impact on the proliferation of lung cancer A549 cell line. Methods miR-21 mimic and inhibitors in lung cancer A549 cell line were transfected by using Lipofectamine 2000 Reagent. After 48 h, Western blot and qRT-PCR were applied to assess the expression of protein and mRNA of Smad7 . MTT assay was used to determine the proliferation influence of the transfected lung cancer A549 cell line. Results Western blot and qRT-PCR showed that A549 cell trans-fected miR-21 mimic exhibited down-regulated Smad7 protein and mRNA expression, and A549 cell transfected miR-21 inhibitor exhibited up-regulated Smad7 protein and mRNA expression. The A549 cell proliferation activity decreased significantly after transfected miR-21 inhibitors. Conclusion miR-21 inhibitors can increase Smad7 pro-tein and mRNA expression, and suppress the proliferation activity of lung cancer A549 cell significantly.

1.15).It had marked difference between the combined group and the ADM group alone(P

Objective To evaluate the efficacy and safety of low-dose dexamethasone pretreatment regimen in prevention of hypersensitive reaction (HR) related to docetaxel in elderly tumor patients. Methods According to the order for admission and the ratio of 3:2, 91 elderly patients with docetaxel weekly therapy were randomly divided into two groups: experimental group and control group. All patients aged from 65 to 82 years with a median age of 68 years old. There were 54 patients in the experimental group and 37 patients in the control group. In the experimental group, patients received oral dexamethasone 4. 5 mg once daily on 1 day before treatment, the day of treatment and continuing for 3 days after treatment, while patients received 8 mg twice daily in the control group. All patients were scored according to MCIRS by the physician. The side effects were evaluated by NCI-CTCAE3.0. Results Four cases in the experimental group (7.4 %) and three cases in the control group (8. 1%) occurred HR, and there was no significant statistical difference (P=1. 000). Conclusions The low dose dexamethasone is efficient and safe compared with the conventional dose dexamethasone, and there is no significant difference in HR incidence between two groups.

Small cell lung cancer is a special type of neuroendocrine tumor in the lungs,which has a poor therapeutic effect,and a short time for resistance to relapse,recurrence and distant metastasis.Therefore,searching for readily available predictive parameters is important for clinical treatment strategy.Some indicators of blood cell parameters have been extensively studied in malignant tumors such as non-small cell lung cancer,breast cancer,gastric cancer and colorectal cancer.In-depth understanding of the role of blood cell parameters in small cell lung cancer and its possible mechanisms are of great value in predicting the curative effect and prognosis of small cell lung cancer.

Objective:According lung adenocarcinoma(LUAD)ferroptosis and non-coding RNA in patients with a long-chain(lncRNA)correlation,binding immunophenotyping constructing new risk rating model to assess the prognosis of LUAD patients.Methods:Based on bioinformatics technology,download the transcriptome data and clinical data of LUAD samples from the TCGA database,obtain genes related to ferroptosis from the FreeDb database,and used"caret"package to screen 504 cases of LUAD samples and randomly divided into training set and validation set according to the ratios of 50%and 50%.Pearson correlation analysis and univariate-factor Cox regression were used to screen ferroptosis-related lncRNA related to the prognosis of LUAD,and the"Conen-susClusterPlus"package of R software was used.Immune correlation analysis with CIBERSORT software,LASSO regression analysis to establish ferroptosis-related lncRNA model,receiver operating characteristic(ROC)curve and area under the curve(AUC)to test the performance of the prognostic model,and verified by validation set.Results:Univariate factor Cox and LASSO regression analysis constructed nine risk scoring models composed of lncRNA related to ferroptosis.Both univariate and multivariate Cox regression analy-sis showed that this prognostic model can be used as an independent prognostic factor(P<0.001).The model had good prediction performance in training set,internal validation set and external validation set.Conclusion:The risk score model of LUAD patients constructed in this study can be used as a new independent prognostic evaluation method,or it may have further application value.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective : To analyze the overall survival( OS) of sequential osimertinib treatment in patients with epidermal growth factor receptor(EGFR) exon 20 T790M mutant advanced non⁃small cell lung cancer(NSCLC) and risk factors of the efficacy of sequential osimertinib treatment. Methods : The data of 138 advanced NSCLC patients with acquired EGFR exon 20 T790M mutation who took sequential osimertinib as second⁃line treatment. KaplanMeier variable was used for survival analysis. The Log⁃rank method was used for univariate analysis. The COX risk regression model was used for multivariate analysis. The survival status and influencing factors of patients treated with sequential osimertinib were analyzed. Results : At the last follow⁃up , 99 of the 138 patients died. Median progression free survival (PFS1)of first⁃line of first⁃ or second⁃generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR⁃TKIs) was 11 months (95% CI: 10. 1 - 11. 9) ; median PFS2 of osimertinib was 10 months (95% CI: 8. 5 - 11. 5) ; The median PFS with sequential osimertinib treatment was 24 months(95% CI: 21. 7 -26. 3) , the median OS was 32 months(95% CI: 28. 9 - 35. 1) . In univariate and multivariate analysis , PFS1 was an independent prognostic factor for PFS and OS(P < 0. 001) . Conclusion Sequential osimertinib treatment for advanced NSCLC patients with acquired EGFR exon 20 T790M mutation achieved good PFS(24 months) and OS (32 months) .