Integrated Analysis to Obtain Potential Prognostic Signature in Glioblastoma

Glioblastoma multiforme (GBM) is the most malignant and multiple tumors of the central nervous system. The survival rate for GBM patients is less than 15 months. We aimed to uncover the potential mechanism of GBM in tumor microenvironment and provide several candidate biomarkers for GBM prognosis. In this study, ESTIMATE analysis was used to divide the GBM patients into high and low immune or stromal score groups. Microenvironment associated genes were filtered through differential analysis. Weighted gene co-expression network analysis (WGCNA) was performed to correlate the genes and clinical traits. The candidate genes’ functions were annotated by enrichment analyses. The potential prognostic biomarkers were assessed by survival analysis. We obtained 81 immune associated differentially expressed genes (DEGs) for subsequent WGCNA analysis. Ten out of these DEGs were significantly associated with targeted molecular therapy of GBM patients. Three genes (S100A4, FCGR2B, and BIRC3) out of these genes were associated with overall survival and the independent test set testified the result. Here, we obtained three crucial genes that had good prognostic efficacy of GBM and may help to improve the prognostic prediction of GBM.

RNA-Based Therapeutics: Current Developments in Targeted Molecular Therapy of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive cancer that has the highest mortality rate out of all breast cancer subtypes. Conventional clinical treatments targeting ER, PR, and HER2 receptors have been unsuccessful in the treatment of TNBC, which has led to various research efforts in developing new strategies to treat TNBC. Targeted molecular therapy of TNBC utilizes knowledge of key molecular signatures of TNBC that can be effectively modulated to produce a positive therapeutic response. Correspondingly, RNA-based therapeutics represent a novel tool in oncology with their ability to alter intrinsic cancer pathways that contribute to poor patient prognosis. Current RNA-based therapeutics exist as two major areas of investigation—RNA interference (RNAi) and RNA nanotherapy, where RNAi utilizes principles of gene silencing, and RNA nanotherapy utilizes RNA-derived nanoparticles to deliver chemotherapeutics to target cells. RNAi can be further classified as therapeutics utilizing either small interfering RNA (siRNA) or microRNA (miRNA). As the broader field of gene therapy has advanced significantly in recent years, so too have efforts in the development of effective RNA-based therapeutic strategies for treating aggressive cancers, including TNBC. This review will summarize key advances in targeted molecular therapy of TNBC, describing current trends in treatment using RNAi, combination therapies, and recent efforts in RNA immunotherapy, utilizing messenger RNA (mRNA) in the development of cancer vaccines.

Trends in new cancer treatments with targeted molecular therapies before and during the COVID-19 outbreak in Veneto, Italy: A real-world, population-based study.

e18734 Background: The COVID-19 outbreak has had a huge impact on health care services worldwide. Previous studies projected delays in cancer diagnoses and excess mortality for cancer patients as a result of the pandemic. Little is known, however, on the impact of the pandemic on the functioning of cancer services. We aimed to fill this gap by using a region-wide, population-based administrative health care data repository. Methods: We obtained data for patients initiating a targeted molecular therapy during 2017-2020 (January-September, by quarter) in Veneto. Eligible treatments were those with lapatinib, pertuzumab, TDM-1 and trastuzumab for breast cancer; with afatinib, alectinib, crizotinib, erlotinib, gefitinib and osimertinib for lung cancer; with cobimetinib, dabrafenib, trametinib and vemurafenib for melanoma; and with niraparib, olaparib and rucaparib for ovarian cancer. Patients starting more than one targeted molecular therapy in a given calendar year were included only once. We estimated the normalised difference between the number of patients for a given quarter in 2020 and the mean number of patients for the corresponding quarter during 2017-2019. Statistical significance was calculated assuming a type I error probability of 5%. Results: The study included 3,180 patients. In 2020, patients starting a targeted molecular therapy were 361 in the first quarter, 260 in the second quarter and 268 in the third quarter. The normalised difference between the number of treatments in 2020 and the mean number of treatments during 2017-2019 for all cancer types combined was statistically significant only for the first quarter, with more therapies in 2020 than in 2017-2019. In a breakdown by cancer type, differences were unremarkable for breast, lung or ovarian cancer, while there were significantly more treatments for melanoma for all the three quarters in 2020 compared to 2017-2019. Conclusions: We chose to use the rate of initiation of targeted molecular therapies as a proxy for the effectiveness of oncology services in managing cancer patients, because these therapies require that at least pathology and diagnostic facilities are fully operational. The study covered a population of nearly five million people, in a region where universal health coverage is available and where cancer care has been prioritised, by law, over non-cancer related health care services during the COVID-19 outbreak. Our findings suggest that provision of oncology care has not been substantially impacted by the pandemic in Veneto. Of note, label indications were unchanged for these drugs in 2020. The findings are also in line with the priority-based, adapted European Society for Medical Oncology recommendations. Further research is needed to assess whether delays at earlier stages of the route to cancer diagnosis (e.g. GP referrals for specialist care) may have occurred.

Identification of Hub Genes Associated With Clinical Characteristics and Potential Therapy of Diabetic Nephropathy by Bioinformatics Analysis.

Background: To provide molecular markers and potential targeted molecular therapy for diabetic nephropathy by screening hubgenes based on bioinformatic analysis. Results: We found 91 differentially expressed genes (DEGs) between diabetic nephropathy tissues and normal kidney tissues. Majority DEGs were significantly enriched in the extracellular matrix structural constituent, collagen-containing extracellular matrix. KEGG pathway analysis showed that most of DEGs participated in PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications. Five high relevant sub-networks and the top 16 genes according to 12 topological algorithms were screened out and also five co-expressed gene modules were identified by WGCNA. Eventually, 5 hub genes were identified by taking the intersection which might be involved in the progression of DN. And 11 microRNAs were associated with related genes in WebGestalt. Conclusions: We identified five hub genes, namely COL1A2, COL6A3, COL15A1, CLU and LUM, and their related microRNAs(especially miR29 and miR196), which might be used as diagnostic biomarkers and therapeutic targets for diabetic nephropathy.

Current Concepts in Multi-Modality Imaging of Solid Tumor Angiogenesis

There have been rapid advancements in cancer treatment in recent years, including targeted molecular therapy and the emergence of anti-angiogenic agents, which necessitate the need to quickly and accurately assess treatment response. The ideal tool is robust and non-invasive so that the treatment can be rapidly adjusted or discontinued based on efficacy. Since targeted therapies primarily affect tumor angiogenesis, morphological assessment based on tumor size alone may be insufficient, and other imaging modalities and features may be more helpful in assessing response. This review aims to discuss the biological principles of tumor angiogenesis and the multi-modality imaging evaluation of anti-angiogenic therapeutic responses.

What should a surgeon known about genetic background of thyroid cancer

Thyroid cancer is the most common endocrine malignancy, the treatment is multidisciplinary and multimodal. Thyroid tumors are heterogeneous in origin, morphology, biological behavior and therapeutic options. Substantial advances in diagnostic methods for thyroid cancer have led to detection of earlier stages of the disease that have the possibility of targeted therapeutic treatment and improved patient prognosis. In addition to surgical treatment, hormonal suppression and radioiodine therapy, targeted molecular therapy, which requires genetic testing, has come to the fore in recent decades. In the summary, we present an overview of current knowledge on the genetic background of individual types of thyroid carcinomas and the possibilities of therapeuticintervention.