Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer with Brain Metastasis

Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients’ quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work

The role of miR-485-5p/NUDT1 axis in gastric cancer

Abstract Background Cancers can survive the oxidative conditions by upregulating nucleoside diphosphate linked moiety X-type motif 1 (NUDT1). However, the mechanisms underlying gastric carcinogenesis and the dys-regulation of NUDT1 in gastric cancer (GC) remain unknown. Our study aimed to explore the role of NUDT1 and its regulatory pathway by miR-485-5p in GC. Methods Gastric cancer tissues and paired noncancerous tissue samples were collected, and the expression level of NUDT1 and miR-485-5p were detected. Two cohorts from The Cancer Genome Atlas (TCGA) database and another cohort from the Tianjin Medical University Cancer Institute and Hospital were further analyzed. Luciferase assays were performed, and the effects of the miR-485-5p/NUDT1 axis on GC cells and normal gastric cells were determined by subsequent experiments. Results We found that the expression of miR-485-5p was clearly repressed in GC tissues, while NUDT1 expression level was dramatically increased. The overexpression of NUDT1 correlated closely with an increase in invasive depth and a decrease in survival in GC patients. MiR-485-5p could directly bind to the 3′UTR of NUDT1 mRNA and induce its degradation, thus down-regulate its expression. The miR-485-5p/NUDT1 axis could lead to the changes of 8-oxo-dG in GC cells. And the increased expression of NUDT1 resulting from the downregulation of miR-485-5p could accelerate cell proliferation and metastasis in GC. However, the growth and migration of normal gastric cells did not depend on the protection of NUDT1, while the overexpression of NUDT1 could promote malignant transition in normal gastric cells. Conclusions MiR-485-5p acts as a tumor suppressor by targeting NUDT1 in GC. The miR-485-5p/NUDT1 axis is involved in the processes of cell growth and cell motility and plays a key role in the tumorigenesis of GC

Epitope identification for p53R273C mutant

Abstract Background With the rise of immunotherapy based on cancer neoantigen, identification of neoepitopes has become an urgent problem to be solved. The TP53 R273C mutation is one of the hotspot mutations of TP53, however, the immunogenicity of this mutation is not yet clear. The aim of this study is to identify potential epitopes for p53R273C mutant. Methods In this study, bioinformatic methods, peptide exchange assay, and peptide‐immunized human leukocyte antigen (HLA) transgenic mouse model were used to explore the immunogenicity of this mutation. Results Peptides with higher affinity to common HLA‐A alleles (A*11:01, A*02:01) were discovered by computational prediction. All the 8–11 mer peptides contain the mutation site were synthesized and soluble peptides were used in the peptide exchange assay. However, the exchange efficiencies of these predicted peptides to HLAs were lower. Fortunately, other peptides with higher exchange efficiency were discovered. Then, the immunogenicity of these peptides was validated with the HLA‐A2 transgenic mice model. Conclusion We identified three potential neoepitopes of p53R273C for HLA‐A*02:01, one potential neoepitope for HLA‐A*11:01 and no neoepitope for HLA‐A*24:02

Nab-Paclitaxel in combination with Cisplatin Versus Docetaxel Plus Cisplatin as First-Line Therapy in Non-small Cell Lung Cancer

Abstract Albumin-bound paclitaxel (nab-PC) and docetaxel both produced favorable efficacy and safety as first-line therapy in advanced non-small cell lung cancer (NSCLC). However, the comparison between nab-PC and docetaxel remained unclear until now. This retrospective study aimed to compare the efficacy and safety of nab-PC/cisplatin with docetaxel/cisplatin as first-line therapy in advanced NSCLC. 271 patients with advanced NSCLC, who received either nab-PC (55 patients) or docetaxel (216 patients) were reviewed from 2012 to 2016. The primary endpoint was objective overall response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety profiles. Nab-PC presented a significantly higher ORR than docetaxel (47.3% vs 31.9%; P = 0.033). The difference of ORR was more significantly remarkable in patients with squamous histology (58.3% vs 29.0%; P = 0.007). Additionally, the DCR of nab-PC was significantly higher than docetaxel. Patients in nab-PC group had a trend toward improved PFS and OS compared with patients in docetaxel group, but this didn’t reach statistical significance. Grade ≥ 3 neutropenia was less in nab-PC group, while Grade ≥ 3 anemia and thrombocytopenia were less in docetaxel group. Nab-PC/cisplatin as first-line therapy, produced significantly higher efficacy and reduced neutropenia than docetaxel/cisplatin in advanced NSCLC

Pretreatment lactate dehydrogenase may predict outcome of advanced non small‐cell lung cancer patients treated with immune checkpoint inhibitors: A meta‐analysis

Abstract The main aim of this study is to investigate whether baseline lactate dehydrogenase (LDH) is associated with the clinical outcome of non small‐cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). We searched Pubmed, the Cochrane Central library and Embase for peripheral blood biomarker of LDH in advanced NSCLC patients treated with ICIs. We extracted the hazard ratio (HR) with 95% confidence interval (CI) for the progression free survival (PFS) and overall survival (OS) and performed meta‐analysis of HR. Pooled estimates of treatment outcomes were calculated by stata 15.1. Six studies with 1136 patients were included in this study. The pooled results of univariate analysis suggested that an elevated pretreatment LDH level was correlated with significant shorter PFS (HR = 1.53, 95% CI 1.27‐1.83, P < 0.001) and OS (HR = 2.11, 95% CI 1.43‐3.11, P < 0.001). The association remained significant in the multivariate analysis that elevated pretreatment LDH level was associated with poor PFS (HR = 1.62, 95% CI 1.26‐2.08, P < 0.001) and OS (HR = 2.38, 95% CI 1.37‐4.12, P = 0.002). A high pretreatment LDH level was significantly correlated with shorter PFS and OS. Pretreatment LDH may serve as a predictive biomarker for advanced NSCLC patients treated with ICIs

miR-409 Inhibits Human Non-Small-Cell Lung Cancer Progression by Directly Targeting SPIN1

Lung cancers, the leading cause of cancer mortality worldwide, are characterized by a high metastatic potential. Growing evidence reveals that Spindlin 1 (SPIN1) is involved in tumor progression and carcinogenesis. However, the role of SPIN1 in non-small-cell lung cancer (NSCLC) and the molecular mechanisms underlying SPIN1 in human NSCLC remain undetermined. Here we examined the function of SPIN1 in human NSCLC and found that the expression of SPIN1 was closely correlated with the overall survival and poor prognosis of NSCLC patients. Aberrant regulation of microRNAs (miRNAs) has an important role in cancer progression. We revealed that miR-409 inhibits the expression of SPIN1 by binding directly to the 3′ UTR of SPIN1 using dual-luciferase reporter assays. Overexpression of miR-409 significantly suppressed cell migration, growth, and proliferation by inhibiting SPIN1 in vitro and in vivo. SPIN1 overexpression in miR-409-transfected NSCLC cells effectively rescued the suppression of cell migration, growth, and proliferation regulated by miR-409. miR-409 regulates the PI3K/AKT (protein kinase B) pathway in NSCLC. Moreover, clinical data showed that NSCLC patients with high levels of miR-409 experienced significantly better survival. miR-409 expression was also negatively associated with SPIN1 expression. Taken together, these findings highlight that the miR-409/SPIN1 axis is a useful pleiotropic regulatory network and could predict the metastatic potential in NSCLC patients early, indicating the possibility that miR-409 and SPIN1 might be attractive prognostic markers for treating NSCLC patients. Keywords: non-small lung cancer, NSCLC, miR-409, SPIN1, therap