scholarly journals Further Understanding of High-Grade Serous Ovarian Carcinogenesis: Potential Therapeutic Targets

2020 ◽  
Vol Volume 12 ◽  
pp. 10423-10437
Author(s):  
Ioannis A Voutsadakis
Keyword(s):  
Therapeutic Targets ◽  
High Grade ◽  
Ovarian Carcinogenesis

scholarly journals EPCO-23. COMPARATIVE TRANSCRIPTOMICS TO IDENTIFY TARGETED THERAPY CANDIDATES IN HIGH GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii74-ii74
Author(s):  
Kelsey Hundley ◽  
Olena Vaske ◽  
Geoff Lyle ◽  
Katrina Learned ◽  
Holly Beale ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Therapeutic Targets ◽  
High Grade Glioma ◽  
Comparative Transcriptomics ◽  
Potential Candidate ◽  
High Grade ◽  
Illumina Hiseq ◽  
Li Fraumeni Syndrome ◽  
Statistical Framework ◽  
Genomic Characterization

Abstract Genomic characterization is often used for the identification of therapeutic targets in tumors. Recently, comparative transcriptomics has begun to be utilized for this purpose. In this pilot, we compare the transcriptome of a patient with recurrent high grade glioma (HGG) to our cohort to identify potential therapies. We reviewed transcriptomic profiles from patients who had resection of HGG at our institution over the past year as well as the UCSC cancer compendium. Briefly, tumor RNA was extracted from embedded tumor tissue sections with tumor cellularity higher than 20%. RNA libraries were sequenced to obtain approximately 65 million reads on an Illumina HiSeq 4000 System utilizing patterned flow cell technology. The RNA profile of a 24 male with Li-Fraumeni syndrome and recurrent HGG with leptomeningeal spread underwent comparative transcriptomics to identify targets. A Bayesian statistical framework for gene expression outlier detection was used. These comparisons allowed for the identification of genes and pathways that are significantly overexpressed. Our internal HGG cohort consisted of 44 adult patients and was evenly distributed among the 4 HGG Verhaak subtypes. Our patient of interest had druggable outlier expression in HDAC1, STAT1 and STAT2 in comparison to our internal cohort indicating vorinostat and ruxolitinib as potential therapies, respectively. We then compared our patient of interest to 12,747 patients in the cancer compendium and STAT2 expression was high but not an outlier. In comparison to 738 glioma samples, STAT1 and STAT2 were outliers but not HDAC1 again indicating ruxolitinib as a potential targeted therapy. The patient did not have outlier expression in notch transcriptional targets or immune checkpoint biomarkers when compared to all cohorts. In conclusion, comparative Transcriptomics can identify therapeutic targets in a patient with recurrent HGG even in small cohorts. In our pilot, we identified ruxolitinib as a potential candidate to treat leptomeningeal recurrence.

scholarly journals HG-10 * HYPOXIA PATHWAY DRIVEN BY HIF-1ALPHA ARE PREDOMINANTLY INVOLVED IN PEDIATRIC HIGH GRADE GLIOMA AND REPRESENT PROMISING THERAPEUTIC TARGETS

2015 ◽  
Vol 17 (suppl 3) ◽  
pp. iii12-iii12
Author(s):  
C. Lasthaus ◽  
M. Litzler ◽  
C. Bour ◽  
D. Guenot ◽  
N. Entz-Werle
Keyword(s):  
Therapeutic Targets ◽  
High Grade Glioma ◽  
High Grade ◽  
Pediatric High Grade Glioma

scholarly journals Ion Channels as Therapeutic Targets in High Grade Gliomas

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3068
Author(s):  
Michaela Griffin ◽  
Raheela Khan ◽  
Surajit Basu ◽  
Stuart Smith
Keyword(s):  
Ion Channels ◽  
Treatment Options ◽  
Cell Cycle Control ◽  
Therapeutic Targets ◽  
High Grade ◽  
Neoplastic Progression ◽  
Invasion And Migration ◽  
Average Survival ◽  
High Grade Gliomas ◽  
And Migration

Glioblastoma multiforme (GBM) is a lethal brain cancer with an average survival of 14–15 months even with exhaustive treatment. High grade gliomas (HGG) represent the leading cause of CNS cancer-related death in children and adults due to the aggressive nature of the tumour and limited treatment options. The scarcity of treatment available for GBM has opened the field to new modalities such as electrotherapy. Previous studies have identified the clinical benefit of electrotherapy in combination with chemotherapeutics, however the mechanistic action is unclear. Increasing evidence indicates that not only are ion channels key in regulating electrical signaling and membrane potential of excitable cells, they perform a crucial role in the development and neoplastic progression of brain tumours. Unlike other tissue types, neural tissue is intrinsically electrically active and reliant on ion channels and their function. Ion channels are essential in cell cycle control, invasion and migration of cancer cells and therefore present as valuable therapeutic targets. This review aims to discuss the role that ion channels hold in gliomagenesis and whether we can target and exploit these channels to provide new therapeutic targets and whether ion channels hold the mechanistic key to the newfound success of electrotherapies.

scholarly journals Patient-derived cell line models revealed therapeutic targets and molecular mechanisms underlying disease progression of high grade serous ovarian cancer

2019 ◽  
Vol 459 ◽  
pp. 1-12 ◽  
Author(s):  
Caroline Kreuzinger ◽  
Isabel von der Decken ◽  
Andrea Wolf ◽  
Magdalena Gamperl ◽  
Julia Koller ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Underlying Disease ◽  
High Grade ◽  
Serous Ovarian Cancer

scholarly journals Integrin-α10 Dependency Identifies RAC and RICTOR as Therapeutic Targets in High-Grade Myxofibrosarcoma

2016 ◽  
Vol 6 (10) ◽  
pp. 1148-1165 ◽  
Author(s):  
Tomoyo Okada ◽  
Ann Y. Lee ◽  
Li-Xuan Qin ◽  
Narasimhan Agaram ◽  
Takahiro Mimae ◽  
...  
Keyword(s):  
Therapeutic Targets ◽  
High Grade

scholarly journals ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers

2014 ◽  
Vol 111 (41) ◽  
pp. 14788-14793 ◽  
Author(s):  
A. Augustyn ◽  
M. Borromeo ◽  
T. Wang ◽  
J. Fujimoto ◽  
C. Shao ◽  
...  
Keyword(s):  
Therapeutic Targets ◽  
High Grade ◽  
Lung Cancers

scholarly journals A Unique Immune-Related Gene Signature Represents Advanced Liver Fibrosis and Reveals Potential Therapeutic Targets

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 180
Author(s):  
Pil-Soo Sung ◽  
Chang-Min Kim ◽  
Jung-Hoon Cha ◽  
Jin-Young Park ◽  
Yun-Suk Yu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Meta Analysis ◽  
Therapeutic Targets ◽  
Gene Signature ◽  
Chronic Liver ◽  
High Grade ◽  
Related Gene ◽  
Chronic Liver Diseases ◽  
Immune Related Gene ◽  
Advanced Liver Fibrosis

Innate and adaptive immune responses are critically associated with the progression of fibrosis in chronic liver diseases. In this study, we aim to identify a unique immune-related gene signature representing advanced liver fibrosis and to reveal potential therapeutic targets. Seventy-seven snap-frozen liver tissues with various chronic liver diseases at different fibrosis stages (1: n = 12, 2: n = 12, 3: n = 25, 4: n = 28) were subjected to expression analyses. Gene expression analysis was performed using the nCounter PanCancer Immune Profiling Panel (NanoString Technologies, Seattle, WA, USA). Biological meta-analysis was performed using the CBS Probe PINGSTM (CbsBioscience, Daejeon, Korea). Using non-tumor tissues from surgically resected specimens, we identified the immune-related, five-gene signature (CHIT1_FCER1G_OSM_VEGFA_ZAP70) that reliably differentiated patients with low- (F1 and F2) and high-grade fibrosis (F3 and F4; accuracy = 94.8%, specificity = 91.7%, sensitivity = 96.23%). The signature was independent of all pathological and clinical features and was independently associated with high-grade fibrosis using multivariate analysis. Among these genes, the expression of inflammation-associated FCER1G, OSM, VEGFA, and ZAP70 was lower in high-grade fibrosis than in low-grade fibrosis, whereas CHIT1 expression, which is associated with fibrogenic activity of macrophages, was higher in high-grade fibrosis. Meta-analysis revealed that STAT3, a potential druggable target, highly interacts with the five-gene signature. Overall, we identified an immune gene signature that reliably predicts advanced fibrosis in chronic liver disease. This signature revealed potential immune therapeutic targets to ameliorate liver fibrosis.

scholarly journals Fusion Genes Altered in Adult Malignant Gliomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Gan You ◽  
Xing Fan ◽  
Huimin Hu ◽  
Tao Jiang ◽  
Clark C. Chen
Keyword(s):  
Genetic Background ◽  
Molecular Genetic ◽  
Malignant Gliomas ◽  
Therapeutic Targets ◽  
High Grade ◽  
Gene Fusions ◽  
Fusion Genes ◽  
High Grade Gliomas ◽  
The Many

Malignant gliomas are highly heterogeneous brain tumors in molecular genetic background. Despite the many recent advances in the understanding of this disease, patients with adult high-grade gliomas retain a notoriously poor prognosis. Fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets to date. Understanding the gene fusions and how they regulate oncogenesis and malignant progression will contribute to explore new approaches for personalized treatment. By now, studies on gene fusions in gliomas remain limited. However, some current clinical trials targeting fusion genes have presented exciting preliminary findings. The aim of this review is to summarize all the reported fusion genes in high-grade gliomas so far, discuss the characterization of some of the most popular gene fusions occurring in malignant gliomas, as well as their function in tumorigenesis, and the underlying clinical implication as therapeutic targets.

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