Research Progress on Combination of Radiotherapy and Immunotherapy on Advanced Non-small Cell Lung Cancer with Negative Driver Genes / 肿瘤防治研究

A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes.

Mutation Genes in Common Tumors of Digestive System and Druggability of New Targets / 肿瘤防治研究

Objective To establish a druggability evaluation method for new targets of anti-tumor drugs by analyzing the mutation genes of common tumors in the digestive system. Methods We collected the mutant gene data of the five common tumors of the digestive system (esophageal cancer, gastric cancer, colorectal cancer, liver cancer and pancreatic cancer) in the Integrative Onco Genomics database, and screened out the genes with higher mutation rates in each tumor. We evaluated the druggability of these genes or their encoded proteins, and discovered the potential targets for the new anti-tumor drugs. Results A total of five tumors, 35 cohorts and 5445 tumor samples were collected in this study. The top 10 mutation genes were selected for further analysis. The canSAR database was used to analyze the druggability of unpublished mutant genes or their encoded proteins, and a total of 17 potential therapeutic drug targets were screened out. Conclusion A method for evaluating druggability of targets based on mutant genes or their encoded protein is established in this study. The application of this method can provide a reference for discovering new anti-tumor therapeutic target, saving the cost and time of target screening in new drug development.

Heritable genomic diversity in breast cancer driver genes and associations with risk in a Chilean population

BACKGROUND: Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families. METHODS: The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay. RESULTS: Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0-1.6] p = 0.02 and OR = 1.5 [95% CI 1.0-2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0-1.7] p = 0.02 and OR = 1.3 [95% CI 1.0-1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0-3.1] p = 0.03 and OR = 1.9 [95% CI 1.1-3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002). CONCLUSIONS: Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.

Research progress in immune checkpoint inhibitors in the treatment of oncogenedriven advanced nonsmall cell lung cancer / 中南大学学报(医学版)

The clinical application of immune checkpoint inhibitors (ICIs) lead to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC), but the efficacy of ICIs in oncogene-driven NSCLC is controversial. Existing research shows that the efficacy of ICIs may be related to different types of driver genes, programmed cell death-ligand 1 (PD-L1) level, and tumor mutational burden (TMB). It may involved in other factors, such as clinical characteristics, and immune cell density. ICIs monotherapy or combination therapy may play a role in a subset of oncogene-driven NSCLC patients, but further studies are needed to select these patients, which may be an important direction for the future development of advanced NSCLC.

C: Consensus Cancer Driver Gene Caller / 基因组蛋白质组与生物信息学报·英文版

Next-generation sequencing has allowed identification of millions of somatic mutations in human cancer cells. A key challenge in interpreting cancer genomes is to distinguish drivers of cancer development among available genetic mutations. To address this issue, we present the first web-based application, consensus cancer driver gene caller (C), to identify the consensus driver genes using six different complementary strategies, i.e., frequency-based, machine learning-based, functional bias-based, clustering-based, statistics model-based, and network-based strategies. This application allows users to specify customized operations when calling driver genes, and provides solid statistical evaluations and interpretable visualizations on the integration results. C is implemented in Python and is freely available for public use at http://drivergene.rwebox.com/c3.

Advances on Recognizing and Managing Tumor Heterogeneity / 中国肺癌杂志

Tumor heterogeneity is one of the characteristics of malignant tumors, which can cause differences in tumor growth rate, invasion, migration, drug sensitivity and prognosis. Discoveries and development upon on tumor-driver genes and targeted therapy paved the way on dealing with cancer diagnosis and treatment. However, the existence of tumor heterogeneity makes malignant tumor more hardly to overcome. It is generally present and far more complicated during the process of cancer recurrence, development and evolution. Thus, it has becoming key areas in precision medicine regarding to designing optimal therapeutic approaches targeting the mechanisms and phenotypes of tumor heterogeneity, based on novel detecting techniques and new concepts and theory. This review summarized the current references on tumor heterogeneity, in order to better understand the function and mechanisms, and eventually manage tumor heterogeneity through various methods.
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Driver genes and targeted drugs in lung cancer / 国际肿瘤学杂志

With the development of molecular biology of cancer,molecular targeted therapy which tar-geted the driver genes in lung cancer has become an inevitable part of the treatment of advanced lung cancer. The most successful examples of targeted therapy are targeting epidermal growth factor receptor (EGFR)and anaplastic lymphoma kinase (ALK).More and more driver genes have been discovered,including ROS1 gene fusion,fibroblast growth factor receptor 1 amplification,KRAS,BRAF,PIK3CA gene mutation and so on.It is meaningful for guiding the treatment of lung cancer that defines the mutation incidence and clinical significance of driver genes in lung cancer.

Integrated genomic analysis-based identification of core pathways and driver genes associated with colorectal carcinoma / 第二军医大学学报

Objective To investigate the core pathways and driver genes associated with development of colorectal carcinoma (CRC). Methods Meta-analysis was employed to screen differently expressed genes between CRC and the adjacent normal mucosa in 5 studies. ComBat was used to comoine tKe gene data of the 5 studies and then the differently expressed genes were used to construct a stable co-expression network in CRC using PCIT software. Cf inder software was used to extract the core sub-networks of the constructed coexpression network, and Gather software was used for functional enrichment analysis of the core subnetworks. Finally, those genes with up-regulation and DNA gain in CRC or down-regulation and DNA loss were identified as driver genes. Results Our meta-analysis found 2 073 differently expressed genes between CRC and the adjacent normal mucosa, including 1 174 up-regulated and 899 down-regulated in 5 the CRC studies. A coexpression network was constructed with those differently expressed genes it had 798 nodes, 1 462 edges, and 22 core subnetworks. The largest subnetwork consisted 77 genes and 436 edges, and the function mainly involved cell cycle and proliferation regulation, with the driver genes including UBE2C, MYBL2, FAM83D, AURKA and TPX2. Conclusion Cell cycle and proliferation pathways are the core ones in the development of CRC, and 77 genes including UBE2C and AURKA are the driver genes of the pathways.

Molecular targeting therapy for gastric cancer / 医学研究生学报

Gastric cancer is the fifth most common cancer and the third leading cause of death globally .Apart from the suc-cessful phase Ⅲclinical trial of trastuzumab and Ramucirumab , other targeted therapies in gastric cancer ( GC) have fallen short or still in early clinical development .In this review, we will summarize the most up to date information on many of the potential actionabledriver genesin gastric cancer and the importance of using the optimal diagnostic test to select for these molecularly defined patients . We focus on the following aspects:HER-2, EGFR, FGFR, MET, IGF-1R and VEGF.