Individual therapy is the current trend of treatment in non-small cell lung cancer patient.However, we still face many questions such as what is the individual therapy, why we need individual therapy,which biomarker could be used to guide the individual therapy and how to undergo individual therapy in nonsmall cell lung cancer patient. This article will give a review to answer these questions.

Individualized therapy is the current trend of treatment in advanced non-small cell lung cancer, the key of individualized therapy is to administrer different treatment options through different biological markers or clinical markers. Currently, biological markers include EGFR protein expression, EGFR mutations, EGFR gene copy, k-ras mutation, EML4-ALK gene fusion, C-MET gene. Clinical markers include rash, pathological types, etc. This article will give a review about those biomarkers.

Chemokines are a group of small molecules that cause the directed migration of cells. In lung cancer, chemokines involve in the regulation of tumor cell growth, angiogenesis, anti-tumor immunity and remote metastasis, which provides a novel therapeutic target for lung cancer.

Objective:To construct RNA interference plasmid specific for integrin β1 gene, and to explore the effects of inhibition of integrin β1 protein expression on the biological behavior of non-small cell lung carcinoma(NSCLC) cells. Methods:Genomic sequences of integrin β1 gene was retrieved from GenBank, and cDNA encoding small hairpin RNA(shRNA) for integrin β1 was designed and named as 17-2. A non-specific sequence was designed as negative control and named as N. The cDNA was synthesized and inserted into plasmids pUC19. Recombinant plasmids were then transformed into competent E.coli. The positive clones were selected and recombinant plasmids were extracted.The two shRNA vectors were transfected into NSCLC cell line PC-9/AB2 mediated by lipofectAMINE 2000. The stably transfec-ted cell clones were selected by G418 screening. Fluorescence microscope, real-time fluorescent quantitative (RFQ)-PCR, and Western blotting were performed to examine integrin β1 mRNA and protein expressions.Cell scratch test and adhesion test were used to detect the influences of silencing integrin β1 on cell migration and adhesion capacity. Results:The stably transfected 17.2 cell clones and N cell clones were screened by G418. The green fluorescence-staining cells were observed in full-field under fluorescence microscope. The level of integrin β1 was significantly down-regulated in 17-2 group compared with N group and primary PC-9/AB2 cells.Scratch test and adhesion test showed that the migration and adhesion capacity of PC-9/AB2 cells was significantly reduced after silencing integrin β1. Conclusion:This study successfully constructed integrin β1 specific shRNA expression vector. The expression of integrin β1 was significantly silenced in NSCLC cells transfected with that vecton. Silencing integrin β1 can significantly reduce the migration and adhesion capacity of NSCLC cells.

Objective:To evaluate the relationship between erlotinib-induced skin rash and clinical outcome and explore the effective way to prevent skin rash. Methods:The data from 76 non-small cell lung cancer(NSCLC) patients who experienced erlotinib-induced skin rash from Dec 2005 to Sep 2008 were collected. All the patients were confirmed with NSCLC by pathological and cytological examination and received erlotinib 150 mg/d till they had progressive disease or intolerable adverse reaction. The severity of skin rash was recorded and graded according to National Cancer Institute-Common Toxicity Criteria (NCI-CTC). The therapeutic outcome of skin rash was observed. Results:The skin rash develops as early as 3 days after commencement of erlotinib therapy, with median onset at 8 days. Twenty-seven (35.5%) patients experienced grade 1 skin rash, 44 patients (57.9%) had grade 2 and 5 cases (6.6%) had grade 3 skin rash. A statistically significant correlation was observed between skin rash and erlotinib therapy. The disease-controlling rate was 63.0% for grade 1 skin rash patients including 5 cases with partial remission and 12 cases with stable disease and 91.8% for grade 2/3 skin rash patients including 32 cases with partial remission and 13 cases with stable disease (P<0.05). The median time to progression(TTP) and median overall survival(OS) were prolonged in patients experienced grade 2/3 skin rash compared with those in patients with grade 1 skin rash (TTP: 5.1 months vs 9.7 months, P<0.01; OS: 10.0 months vs 14.6 months, P<0.01). The skin rash was alleviated in 60 out of 76 patients (78.9%). Conclusion:Skin rash is a potent surrogate marker of favorable outcome in patients who received erlotinib treatment. It was tolerable to most patients. Appropriate therapy may be useful in decreasing the severity of skin rash.

Objective:To make a prospective study on the effectiveness and safety of toremifene (TOR) combined with novelbine/cisplatin (NP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose first line platinum-based chemotherapy was failure. Methods:Forty-four patients with stage ⅡB-Ⅳ NSCLC, who failed in the first line cisplatin-based chemotherapy from January 2004 to February 2006, were enrolled in this study. All the patients received TOR combined with NP second line chemotherapy for two cycles. The response rate and adverse reaction were evaluated. The survival rate was analyzed.Results:The 44 patients received average 1.8 cycles of chemotherapy (1-3 cycles). The response of 37 patients could be evaluated including 21 patients who received NP regimen before and 16 patients who received platinum-based chemotherapy. After second line therapy, 4 of the 37 patients had partial response (PR), 19 had stable disease (SD), 14 had progressive disease (PD), and no patient had complete response (CR). The total response rate (CR+PR) was 10.8% (4/37). The disease-controlling rate (CR+PR+SD) was 62.2% (23/37). The response rate and disease-controlling rate of squamous cell lung cancer (SCC) were 27.3% (3/12) and 72.7% (8/12), which were significantly higher than adenocarcinoma [0% (0/18) and 44.4% (8/18), P<0.05]. The median survival time was 8.2 months, the median time for SD was 4.0 months (1.0-10.2 months), and the 1-year survival rate was 24.4%. The median survival time and 1-year survival rate of SCC patients had no significant difference compared with adenocarcinoma patients (9.2 vs 7.1 months; 33.3% vs 27.7%, P＝0.72). There was no significant difference in survival rate between male and female patients. One patient stopped therapy for liver function injury (hyperbilirubinemia). The adverse reactions induced by chemotherapy mainly included gastrointestinal reaction, bone marrow suppression, and liver function injury. No serious adverse reaction occurred. Conclusion:The clinical efficacy of second line TOR combined with NP regimen is similar with the first line regimen for NSCLC patients, especially for SCC patients. The frequency of adverse reaction is not increased.

Purpose:To investigate prognostic effects of ex pressions of cyclooxygenase-2(COX-2) and epidermal growth factor receptor(EGFR )in non-small-cell lung cancer(NSCLC).Methods:Expression of COX-2 and EGFR in the resected tumors of 60 patients with NSCLC were detected with the method of immunohistochemistry st aining.We used ?2 test and COX regression analysis to compare difference in e xpressions of COX-2 and EGFR in differentiation grade of squamous and adeno-ca rcinoma cells of the lungs and their relationships with the patients survival in NSCLC.Results:The positive rates for COX-2 were 73% and 33% in adeno carcinoma and squamous carcinoma,respectively.The expression rate was significan tly higher in the adenocarcinoma than in the squamous carcinoma.Expressions of C OX-2 and EGFR in NSCLC were not related to patientsage and sex,differentiation grade of tumor cells,TNM staging,size of promary tumor and lymph nodes metastasi s.Median survival time was 30 months and 16 months in COX-2 expression levels o f “+” and of “++”,34 months and 15 months in EGFR expression levels of “+” and of “++” and was significantly lower than in those without expression of C OX-2 or EGFR(P

0. 05), and were closely correlated to the clinical stage and the curative effect(P 0. 05). Conclusions: VEGF expression was contributes to the tumor neovascularization and tumor metastasis. Local control rate of VEGF positive tumor patients can be increased but their survival can not be prolonged by mono-chemotherapyonly only.

Objective:To construct superparamagnetic iron oxide nanoparticles targeting tumor angiogenesis and evaluate their potential value as contrast agent in magnetic resonance imaging (MRI) .Methods:Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles targeting tumor angiogenesis were prepared by using co-precipitation chemical method. Cyclic RGD(cRGD) containing the sequence of Arg-Gly-Asp were conjugated USPIO nanoparticles by using chemical conjugative method to prepare superparamagnetic imaging agent targeting tumor angiogenic vessles. The physical and chemical properties of cRGD-USPIO nanoparticles were detected. The specific binding capabilities of cRGD-USPIO and USPIO to human lung adenocarcinoma cells (A549) and human umbilical vein endothelial cells (HUVEC) were tested by Prussian blue staining. A549 xenografts were established in nude mice, then USPIO and cRGD-USPIO were injected though tail vein, and the MRI signal enhancement effect of cRGD-USPIO was evaluated.Results:We successfully prepared the cRGD-USPIO nanoparticles. Its core diameter was 5-10 nm and the average diameter was (43.97±10.10) nm and the quality saturation magnetic intensity was 59.94 A·m~2·kg~(-1). Cell-binding test suggested that cRGD-USPIO group showed strengthened positive staining. In vivo MRI experiments showed that signals of tumor were significantly reduced in cRGD-USPIO group than that in USPIO group (P<0.01). Conclusion:The constructed cRGD-USPIO nanoparticles can be developed as a potential tumor-specific MRI contrast agent for the early diagnosis of cancer.

Early diagnosis and screening are of great significance for improving the prognosis of patients with lung cancer. Low-dose helical computed tomography (LDCT) reduces lung cancer mortality by about 20％, making it the most effective screening tool. However, high false-positive rates, costs, and potential harms highlight the need for complementary biomarkers. The diagnostic performance of biomarkers such as noninvasive autoantibody and plasma/serum microRNA (miRNA) were shown in several studies, making them approved for early diagnosis in our country, Europe and the United States, and their role in screening is being explored in ongoing studies.