Adenocarcinoma ; diagnosis ; drug therapy ; genetics ; metabolism ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; metabolism ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Discoidin Domain Receptors ; Glutamates ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; metabolism ; Molecular Diagnostic Techniques ; methods ; Mutation ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Pemetrexed ; Protein Kinase Inhibitors ; therapeutic use ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; genetics ; metabolism ; Receptors, Mitogen ; genetics ; metabolism ; Transcription Factors

Carcinoma, Non-Small-Cell Lung ; genetics ; Exons ; genetics ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; pathology

With the promotion of precision medicine , tumor targeted therapy has entered into a new stage .Developments in molecular biotechnology have contributed to the discovery of numerous novel molecular targets .The advent of new targeted drugs and continuous updating data from large clinical research have provided more options for the precise treatments of lung cancer .This article aims to review the latest progress about targeted therapy and precision medicine in lung cancer .

Background and purpose:The occurrence and development of lung cancer are closely correlated with the immune function in the human body.The patients with malignant tumors have shown a disorder of immune function,especially in terms of loss of cellular immune function.The purpose of this study was to investigate the possible auxiliary effect of sipulin in the treatment of advanced non-small-cell lung cancer(NSCLC).methods: Ninety-three patients were randomly divided into two groups:sipulin group:sipulin plus docetaxel+cisplatin;control group:only administered docetaxel+cisplatin.The leukocyte,haemoglobin and platelet,toxicity of digestive tract,body weight,Karnofsky status and efficacy of those patients were evaluated before and after therapy,respectively.Results: Overall response rates were 46.67% and 30.23%(P=0.023)in sipulin group and control group,respectively.The median survival time was 10.1months versus 8.3 months(P=0.035)in sipulin group and control group,respectively.The 1-year survival rate for sipulin group and control group was 52.9% versus 39.4%(P=0.038),respectively.The clinical efficacy and the frequence of leukocyte reduction were better in sipulin group than in control group,the quality of life and clinical symptom of the patients in sipulin group were improved more significantly than those in control group (P

OBJECTIVETo observe the efficacy, median survival time, time to progression, quality of life and adverse effect of gefitinib (IRESSA) in the treatment for refractory advanced non-small cell lung cancer (NSCLC).

METHODSForty-one patients with stage III b to IV NSCLC who had previously treated with 2-7 cycles of platinum-based chemotherapy were enrolled into the study, 85.4% of the patients had received second line chemotherapy. The regimen was oral intake of gefitinib 250 mg once daily until the disease progression or intolerable toxic reaction occurred. The patients were required to receive tumor assessment before the treatment, one month, two months and every three months after IRESSA administration.

RESULTSAll 41 patients were evaluable for therapeutic effect. Partial response rate (PR), stable disease (SD) and progression of disease (PD) was 43.9% (18/41), 34.1% (14/41) and 22.0% (9/41), respectively. No complete regression was observed. The overall response rate was 43.9% (18/41) with a rate of 42.1% in the male and 45.5% in the female (P > 0.05). The disease control rate (PR + SD) was 78.0% (32/41). Twenty-two of the 41 patients (53.7%, 22/41) were still alive with MST of 10.1 months when the follow-up ended in Nov. 2006. TP and MST of dead patients was 2.7 and 5.0 months, respectively. The rate of symptom improvement was 78% for all patients with MST of 13.3 months for PR patients. The performance status (Karnofsky) was improved (20 +/- 5) after 28-day treatment. III-IV degree toxicity was not observed.

CONCLUSIONIRESSA is effective and safe for the advanced NSCLC patients with poor performance status who previously failed in the second or third line chemotherapy.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Bone Neoplasms ; secondary ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Quality of Life ; Quinazolines ; adverse effects ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Remission Induction ; Survival Rate

OBJECTIVETo construct a recombined phage vaccine and to evaluate the efficiency of this phage vaccine against EGFR-positive tumors.

METHODST7 phage display system was used to display five fragments of the extracellular domain of chicken EGFR. The EGFR was expressed as a fused protein on the surface of the T7 phage 10B capsid protein. The EGFR expression of the phage vaccine was verified by Western-blot analysis. Anti-EGFR antibody was detected by ELISA. Splenic lymphocytes of the immunized mice were separated and used to determine the immunotoxic effect against A431 cells. The phage vaccines were injected into C57 mice 4 times before Lewis lung cancer cells inoculation. Tumor volume was recorded to evaluate the anti-tumor effect of each vaccine.

RESULTSFive phage vaccines inserted with the chicken EGFR gene were successfully constructed. Western blot assay showed that the extracellular domain of chicken EGFR proteins were displayed on the surface of the phage. Specific antibody was induced in the immunized mice, compared with the control group. Splenic lymphocytes of the immunized mice were shown to be immunotoxic against A431 cells. The killing rates of the experimental groups were higher than that of control group (P < 0.001, t-Student test). The highest killing rate was (45.74 +/- 7.21)%. The tumor growth was inhibited in the experimental groups compared with those of control groups (P < 0.05 in C1, C2, C3, C4 groups, P > 0.05 in C5 group).

CONCLUSIONOur results demonstrated that recombined EGFR phage vaccines may be used to induce therapeutic anti-tumor immunity against EGFR-positive tumors.

Animals ; Bacteriophage T7 ; genetics ; Blotting, Western ; Cancer Vaccines ; administration & dosage ; genetics ; immunology ; Capsid Proteins ; genetics ; metabolism ; Carcinoma, Lewis Lung ; immunology ; pathology ; therapy ; Cell Line, Tumor ; Chickens ; Cytotoxicity Tests, Immunologic ; Immunotherapy ; methods ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Random Allocation ; Receptor, Epidermal Growth Factor ; genetics ; immunology ; metabolism ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism

OBJECTIVETo investigate the impact of erlotinib as a second or third line treatment on the symptoms and quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC).

METHODSFifty patients with stage III b and IV NSCLC, treated previously with at least one regimen of platinum-based chemotherapy, received 150 mg of erlotinib orally, once a day till disease progression. QOL was assessed by European Organization for Research and Treatment of Cancer QLQ-C30 and the lung cancer module (QLQ-LC13). The primary end points for QOL analysis were time to deterioration of three common lung cancer symptoms: cough, dyspnea and pain.

RESULTSAmong 47 evaluable cases, there were partial remission (PR) in 18 cases, stable disease (SD) in 21 cases, and progressive disease (PD) in 8 cases. After two cycles of treatment, the mean scores of global QOL and all 5 functioning scales except the cognitive function increased significantly (P < 0.05). Mean scores of major general symptoms, hypodynamia and anorexia, and disease-related symptoms alleviated significantly. Both response rates of five functioning and global QOL were more than 44% after erlotinib treatment. Response rates of major general symptoms and disease-related symptoms varied from 14% to 76%. Patients with complete or partial response likely had improvement in the QOL response (P < 0.05), and the time to major symptom deterioration in those were significantly longer (P < 0.001) than that in patients with stable or even progressive disease.

CONCLUSIONErlotinib is effective to improve not only survival, but also tumor-related symptoms and quality of life in patients with advanced NSCLC previously treated with cisplatin-contained regimens. The improvement in the quality of life is positively correlated with objective tumor response.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Disease Progression ; Erlotinib Hydrochloride ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Quality of Life ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; therapeutic use ; Remission Induction ; Salvage Therapy ; Treatment Failure

OBJECTIVETo investigate mutations of EGFR TK gene in non-small cell lung cancer (NSCLC) and the diagnostic value of the mutations assayed by real-time PCR using TaqMan-MGB probes.

METHODSTyrosine kinase genes of EGFR (exons 18, 19 and 21) were amplified by PCR technology, and sequenced and analyzed by Chromas software in 80 NSCLC patients. Based on the results of sequencing, TaqMan-MGB probes were designed and used to detect the mutations of EGFR by real-time PCR. The results of detected mutations were compared between real-time PCR and direct sequencing. The sensitivity and specificity of real-time PCR using TaqMan-MGB probes were analyzed by adding different number of PC-9 cells (exon 19 deleted EGFR) into A549 cells (Wild-type EGFR).

RESULTSSomatic mutations were identified in the tyrosine kinase domain of the EGFR gene in 21 of 80 NSCLC patients with an incidence rate of 26.3%. In-frame deletions of exon 19 occurred in 13 patients and point mutation occurred in codon 858 (exon 21) in 8 patients. Real-time PCR with the TaqMan MGB probes could detect all the mutations of EGFR found by sequencing. The sensitivity and specificity of the detection of EGFR mutations were both 100%. Real-time PCR with TagMan MGB probes could detect EGFR mutation in as rare as 50 EGFR mutant cells and in a proportion of 10% of mutant cells in a cell population. The mutations were significantly higher in the adenocarcinoma than in non-adenocarcinoma (16/38 vs. 5/42, chi2 = 9.702, P <0.01), in the female patients than in the male patients (14/29 vs. 7/51, chi2 = 11.4, P <0.01) and in non-smokers than in smokers (16/40 vs. 5/40, chi2 = 7.812, P < 0.01). The mutations were not related to patients'age, TNM staging, etc.

CONCLUSIONSomatic mutations of EGFR gene develop in NSCLC and are more common in female, non-smoker and adenocarcinoma patients. Real-time PCR using TaqMan-MGB, which can be used to detect the EGFR gene mutations, is easy to operate and deserves widespread application.

Adenocarcinoma ; genetics ; pathology ; Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Cell Line, Tumor ; Chi-Square Distribution ; Codon ; DNA Mutational Analysis ; DNA Probes ; genetics ; Exons ; Female ; Gene Deletion ; Humans ; Lung Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Polymerase Chain Reaction ; methods ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking

OBJECTIVETo explore the sensitivity of tumor cell lines with acquired resistance to gefitinib to several chemotherapeutic drugs and provide preclinical basis of available chemotherapy regimens after failure of molecular targeted therapy.

METHODSHuman lung adenocarcinoma cell lines PC9 and PC9/G with acquired resistance to gefitinib were cultured in vitro. The sensitivity to chemotherapeutic drugs and inhibition rate of cell proliferation was determined by MTT assay. Effects of drugs on apoptosis and expression of P-170 were determined by flow cytometry. Difference of gene expression profile between PC9 and PC9/G cells was analyzed by DNA microarray. Western blot was used to test the expression of Akt, phospho-Akt and integrin beta1.

RESULTSThe resistance index of PC9/G cells to cisplatin was about 5.4-fold compared with that of PC9 cells. LY294002 may significantly elevate the sensitivity of PC9/G cells to cisplatin (P < 0.05). PC9/G cells were more sensitive to docetaxel than PC9 cells. No significant difference of sensitivity to pemetrexed was found between these two cell lines. Expression level of P-170 in PC9/G cells was lower than that in PC9 cells. In PC9/G cells, the expression of integrin beta1 and DNA healing gene was high and expression of gene during mitosis was low. The level of expression of Akt, phospho-Akt and integrin beta1 in PC9/G cells was higher than that in PC9 cells.

CONCLUSIONIn PC9/G cells, a cell line with acquired resistance to gefitinib, over-expression of PI3K, integrin and DNA restoration gene and continuous activation of PI3K is found to be correlated with resistance to cisplatin. Docetaxel or pemetrexed is a more reasonable choice than cisplatin for treatment of NSCLC patients who failed to respond to EGFR-TKI.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Chromones ; pharmacology ; Drug Resistance, Neoplasm ; Glutamates ; pharmacology ; Guanine ; analogs & derivatives ; pharmacology ; Humans ; Integrin beta1 ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; Morpholines ; pharmacology ; Pemetrexed ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Quinazolines ; pharmacology ; Taxoids ; pharmacology