The role of CSTF2 in cancer: from technology to clinical application.

A protein called cleavage-stimulating factor subunit 2 (CSTF2, additionally called CSTF-64) binds RNA and is needed for the cleavage and polyadenylation of mRNA. CSTF2 is an important component subunit of the cleavage stimulating factor (CSTF), which is located on the X chromosome and encodes 557 amino acids. There is compelling evidence linking elevated CSTF2 expression to the pathological advancement of cancer and on its impact on the clinical aspects of the disease. The progression of cancers, including hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, and pancreatic cancer, is correlated with the upregulation of CSTF2 expression. This review provides a fresh perspective on the investigation of the associations between CSTF2 and various malignancies and highlights current studies on the regulation of CSTF2. In particular, the mechanism of action and potential clinical applications of CSTF2 in cancer suggest that CSTF2 can serve as a new biomarker and individualized treatment target for a variety of cancer types.

The evaluation of efficacy and safety of sunitinib on EGFR-TKI pretreated advanced non-small cell lung cancer patients in China.

BACKGROUND: Sunitinib is an oral multitargeted tyrosine kinase inhibitor (TKI) exhibiting antiagiogenic and antitumor effects. OBJECTIVE: To evaluate the efficacy and potential toxicity of sunitinib therapy in advanced non-small cell lung cancer (NSCLC) patients in China. METHODS: From January 2009 to August 2011, 30 patients with stage IV NSCLC, who were pretreated with the epidermal growth factor receptor (EGFR)-TKIs and then received sunitinib, were retrospectively reviewed. Univariate and multivariate Cox proportional hazard regression analysis was performed to determine the potential prognostic risk factors influencing NSCLC survival. RESULTS: The median progression-free survival (PFS) and median overall survival (OS) of all 30 treated patients was 1.25 months [95% confidence interval (CI): 0.90-1.9 months] and 3.40 months (95% CI: 3.00-6.80 months), respectively. Cox regression analysis suggested that Eastern Cooperative Oncology Group (ECOG) performance status (PS) is predictive of both PFS (P=0.001) and OS (P<0.001). Common adverse events (AEs) included hand-foot syndrome (53.3%), mucositis (40.0%), rash (36.7%) and diarrhea (33.3%). CONCLUSION: No sign of overall clinical benefits of sunitinib was detected in patients with pretreated EGFR-TKIs. Most patients suffered AEs from mild to moderate severity. ECOG PS is highly associated with PFS and OS rate. Further studies in NSCLC are required to determine whether sunitinib is beneficial nor not.

[Analysis of prognostic factors in patients with stage IV lung adenocarcinoma after failure of second-line EGFR-TKIs therapy].

BACKGROUND: The prognostic factors and salvage therapy after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy have brought concerns. This study aims to analyze retrospectively the clinical data of patients with advanced lung adenocarcinoma and explore their prognostic factors. METHODS: Patients with integral clinic dates and staged IV lung adenocarcinoma with performance status (PS) scores from 0 to 2 were enrolled between January 2009 and February 2012 and followed up until death. The primary endpoint was survival time after the failure of EGFR-TKI therapy. RESULTS: A total of 81 patients were enrolled into the study, and the median overall survival time was 9.6 months (QL-QU: 5.4-19.2). Univariate analysis showed that PS score, metastatic status, and the presence of plural effusion were significantly correlated with patient survival time (P<0.05), whereas normal levels of carcinoembryonic antigen after EGFR-TKI therapy and history of operation showed a trend towards longer survival time. Multivariate analysis showed that the PS score, metastatic status, and plural effusion are independent prognostic factors for advanced adenocarcinoma after the failure of targeted therapy (P<0.05). CONCLUSIONS: A PS score from 0 to 1, single metastasis, and none or less plural effusion may attribute to the good outcome of stage IV lung adenocarcinoma and should further undergo chemotherapy.

[Effects of EGFR-TKIs on sequential pemetrexed
for advanced pulmonary adenocarcinoma].

BACKGROUND AND OBJECTIVE: Pemetrexed and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) were used in patients with EGFR mutation to determine their effects. This study analyzed the influence of EGFR-TKIs on pemetrexed by observing the clinical efficacy and toxicity of pemetrexed following responses to EGFR-TKIs. METHODS: Pulmonary adenocarcinoma patients were divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy. All patients received pemetrexed (500 mg/m2) as second (or higher)-line treatment. The Response Evaluation Criteria in Solid Tumors (version 1.0) were used to evaluate the response to pemetrexed. Adverse events were classified based on version 4.0 of the National Cancer Institute Common Toxicity Criteria. RESULTS: There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs group. The disease control rates (DCRs) were 77.2% and 67.9% (P=0.367). The progression free survival (PFS) periods were 5.95 and 3.55 months (P=0.535). The overall survival (OS) periods were 10.10 and 8.24 months (P=0.432). However, these values were not statistically significant. The common toxicities of pemetrexed were hematologic and gastrointestinal (grades I and II). Two patients in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities, which were not observed in the no-EGFR-TKIs group. Both groups had one patient who reduced dosage because of myelosuppression (grade IV). There were five and nine patients in the EGFR-TKIs and no-EGFR-TKIs groups, respectively, who delayed therapy not because of severe toxicities but due to subjective factors. CONCLUSION: The DCRs, PFS periods, and OS periods of the patients administered with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs group, but the differences were not statistically significant. Therefore, sequential pemetrexed administration caused negligible toxicities and can be used in adenocarcinoma therapy following responses to EGFR-TKIs.

[Preliminary results of metabolite in serum and urine of lung cancer patients detected by metabolomics].

BACKGROUND AND OBJECTIVE: Lung cancer is one of the most common cancers worldwide. Thus far, good tumor markers for diagnosing this disease have not been found. Therefore, the discovery of novel biomarkers through the application of new methods has become a hotspot in lung cancer research. The aim of this study is to analyze low-molecular-weight metabolites in the serum and urine samples of lung cancer patients and patients with other lung diseases through metabolomics and to explore potential tumor markers further. METHODS: Both serum and urine samples from 19 lung cancer patients and 15 patients with other lung diseases were subjected to metabolomic analysis using gas chromatography mass spectrometry. Orthogonal to partial least squares discriminant analysis was performed for modeling. Two sample t-test was used to identify differences in metabolite concentrations. RESULTS: A total of 57 metabolites were found in the serum, and 38 metabolites were found in the urine. Multivariate statistical analysis yielded a significant distinction in the metabolic profiles between lung cancer patients and patients with other lung diseases. The t-test results indicated a total of 13 metabolites in the serum and 7 metabolites in the urine with statistically significant differences. CONCLUSIONS: Metabolomics is useful in discriminating between lung cancer and other lung diseases. As a novel approach, it has potential in the diagnosis of lung cancer at molecular level.

[Pemetrexed alone versus pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma].

BACKGROUND AND OBJECTIVE: At present, there is no standard salvage treatment strategies for lung cancer. The aim of this study is to compare the efficacies and safeties of pemetrexed alone with pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma to provide evidences for combination therapy. METHODS: From January 2009 to February 2011, 83 patients with stage IV lung adenocarcinoma received pemetrexed alone (single agent arm, n=47) or pemetrexed combined with oxaliplatin (combination arm, n=36) as salvage therapy. All 83 patients had performance status (PS) scores of 0-2. RESULTS: Eighty-one patients were included in the final analysis. The median progression-free survival (PFS) in the single agent arm was 3.6 months versus 4.1 months in the combination arm (P=0.268). The objective response rate (ORR) was 6.5% versus 20% (P=0.092), and the disease control rate (DCR) was 56.5% versus 65.7% (P=0.493), respectively. The response rates of the hematological and gastrointestinal toxicities in the single agent and combination arms were 33.9% versus 47.2% (P=0.460) and 21.2% versus 25.0% (P=0.213), respectively. CONCLUSIONS: For salvage therapy, pemetrexed combined with oxaliplatin is tolerable in stage IV lung adenocarcinoma patients with good PS scores. Compared with pemetrexed alone, pemetrexed combined with oxaliplatin therapy showed higher response rate, but did not significantly prolong the PFS.