ESDR256 - Metabolic Vulnerabilities as Predictive Biomarkers and Therapeutic Targets in Skin Carcinogenesis

2021 ◽  
Author(s):  
Pauline Michon
Keyword(s):  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Skin Carcinogenesis

scholarly journals 256 Metabolic Vulnerabilities as Predictive Biomarkers and Therapeutic Targets in Skin Carcinogenesis

2021 ◽  
Vol 141 (10) ◽  
pp. S192
Author(s):  
P. Michon ◽  
L. Dousset ◽  
W. Mahfouf ◽  
E. Muzotte ◽  
F. Moisan ◽  
...  
Keyword(s):  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Skin Carcinogenesis

Predictive and prognostic biomarkers with therapeutic targets in colorectal cancer: A 2021 update on current development, evidence, and recommendation

2021 ◽  
pp. 107815522110055
Author(s):  
Clement Chung
Keyword(s):  
Checkpoint Inhibitors ◽  
Therapeutic Targets ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Tumor Location ◽  
Prognostic Biomarkers ◽  
Her2 Gene ◽  
Braf Mutations ◽  
Therapeutic Implications ◽  
Molecular Alterations

Although therapeutically actionable molecular alterations are widely distributed across many cancer types, only a handful of them show evidence of clinical utility and are recommended for routine clinical practice in the management of cancers of colon and rectum (CRC). This 2021 update aims to provide a succinct summary on the use of prognostic and/or predictive biomarkers (expanded RAS, BRAF, microsatellite-high [MSI-H] or deficient mismatch repair [dMMR], neurotrophic tyrosine receptor kinase [ NTRK] fusion genes, and human epidermal growth factor receptor type II [ HER2] gene amplification) associated with CRC. Therapeutic implications of each relevant predictive or prognostic biomarker for patients with CRC are described, along with discussion on new developments on (1) biomarker-driven therapies such as testing of BRAF, MLH1 promoter methylation and MMR germline genes in differentiating sporadic CRC or hereditary conditions such as Lynch syndrome; (2) first-line use of immune checkpoint inhibitors in metastatic CRC; (3) risk stratification and therapy selection based on primary tumor location (left-sided vs. right-sided colon cancer); (3) atypical BRAF mutations; (4) use of EGFR directed therapy in the perioperative oligometastatic disease setting; (5) re-challenge of EGFR directed therapy and (6) personalizing therapy of fluoropyrimidine and irinotecan based on new evidence in pharmacogenomic testing. Data are collected and analyzed from available systematic reviews and meta-analyses of treatments with known therapeutic targets in CRC, which may be associated with predictive and/or prognostic biomarkers. Discussions are presented in an application-based format, with goal to empower pharmacists or other clinicians to gain awareness and understanding in biomarker-driven cancer therapy issues.

scholarly journals Plasma-derived Extracellular Vesicles Contain Predictive Biomarkers and Potential Therapeutic Targets for Myocardial Ischemic (MI) Injury

2016 ◽  
Vol 15 (8) ◽  
pp. 2628-2640 ◽  
Author(s):  
Esther Sok Hwee Cheow ◽  
Woo Chin Cheng ◽  
Chuen Neng Lee ◽  
Dominique de Kleijn ◽  
Vitaly Sorokin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Targets ◽  
Predictive Biomarkers

scholarly journals The Construction and Analysis of the Aberrant lncRNA-miRNA-mRNA Network in Adipose Tissue from Type 2 Diabetes Individuals with Obesity

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Wei Hu ◽  
Yuanlin Ding ◽  
Shu Wang ◽  
Lin Xu ◽  
Haibing Yu
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Biological Pathways ◽  
Differentially Expressed ◽  
Public Health Issue ◽  
Cerna Network

Background. The prevalence of obesity and type 2 diabetes mellitus (T2DM) has become the most serious global public health issue. In recent years, there has been increasing attention to the role of long noncoding RNAs (lncRNAs) in the occurrence and development of obesity and T2DM. The aim of this work was to find new lncRNAs as potential predictive biomarkers or therapeutic targets for obesity and T2DM. Methods. In this study, we identified significant differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) between adipose tissue of individuals with obesity and T2DM and normal adipose tissue (absolute log2FC≥1 and FDR<0.05). Then, the lncRNA-miRNA interactions predicted by miRcode were further screened with a threshold of MIC>0.2. Simultaneously, the mRNA-miRNA interactions were explored by miRWalk 2.0. Finally, a ceRNA network consisting of lncRNAs, miRNAs, and mRNAs was established by integrating lncRNA-miRNA interactions and mRNA-miRNA interactions. Results. Upon comparing adipose tissue from individuals with obesity and T2DM and normal adipose tissues, 364 significant DEmRNAs, including 140 upregulated and 224 downregulated mRNAs, were identified in GSE104674; in addition, 231 significant DEmRNAs, including 146 upregulated and 85 downregulated mRNAs, were identified in GSE133099. GO and KEGG analyses have shown that downregulated DEmRNAs in GSE104674 and GSE133099 were associated with obesity- and T2DM-related biological pathways, such as lipid metabolism, AMPK signaling, and insulin resistance. Furthermore, 28 significant DElncRNAs, including 14 upregulated and 14 downregulated lncRNAs, were found. Based on the predicted lncRNA-miRNA and mRNA-miRNA relationships, we constructed a competitive endogenous RNA (ceRNA) network, including five lncRNAs, ten miRNAs, and 15 mRNAs. KEGG-GSEA analysis revealed that four lncRNAs (FLG-AS1, SNAI3-AS1, AC008147.0, and LINC02015) in the ceRNA network were related to the biological pathways of metabolic diseases. Conclusions. Through ceRNA network analysis, our study identified four new lncRNAs that may be used as potential biomarkers and therapeutic targets of obesity and T2DM, thus laying a foundation for future clinical studies.

Identification of candidate biomarkers of therapeutic response to docetaxel in hormone-refractory prostate cancer by proteomic profiling

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11010-11010
Author(s):  
L. Horvath ◽  
L. Zhao ◽  
B. Lee ◽  
D. Brown ◽  
M. Molloy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Plasma Levels ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Protein Profiling ◽  
Hormone Refractory Prostate Cancer ◽  
Psa Response ◽  
Pc3 Cells ◽  
Hormone Refractory

11010 Background: Docetaxel (DTX)-based chemotherapy improves symptoms and survival in men with advanced hormone-refractory prostate cancer (HRPC). However, approximately 50% of patients do not respond to DTX but are exposed to significant toxicity without direct benefit. This study aimed to identify novel therapeutic targets and predictive biomarkers of DTX-resistance in HRPC. Methods: Protein profiling using iTRAQ mass spectrometry compared the PC3-Rx and DTX-sensitive PC3 cells and DTX-resistant PC3-Rx developed by DTX dose-escalation. Functional validation experiments were performed using recombinant protein treatment and siRNA knockdown experiments. Plasma/serum samples were collected from 41 men with metastatic HRPC treated with DTX-based chemotherapy (36 with paired samples pre- and post- cycle 1 DTX). Serum/plasma levels of MIC-1 were measured by ELISA. The association between MIC-1 levels, PSA response and overall survival (OS) were assessed by non-parametric tests and Kaplan-Meier survival analysis. Results: The IC50 for DTX in PC3-Rx was 10-fold higher than that in parent PC-3 cells. Protein profiling identified that MIC-1 levels were elevated 2.4 fold and AGR2 decreased 2.4 fold in DTX resistant cells. Knockdown of AGR2 expression in PC3 cells resulted in increased DTX resistance (p=0.03). PC-3 cells treated with recombinant MIC-1 also became resistant to DTX (p=0.001). Conversely, treating PC3-Rx cells with MIC1-siRNA restored sensitivity to DTX (p=0.002). In HRPC patients, pre-treatment MIC-1 levels did not correlate with PSA response to treatment (p=0.6). In contrast, increased serum/plasma levels of MIC-1 after cycle one of chemotherapy were associated with DTX resistance (p=0.006) and shorter overall survival (p=0.002). Conclusions: These results suggest that both AGR2 and MIC-1 play a role in DTX resistance in HRPC. Furthermore, changes in serum/plasma MIC-1 levels are associated with DTX resistance in a correlative human cohort. While a larger study is needed to validate these findings, the data provide evidence that MIC-1 as a potential predictive biomarker and both MIC-1 and AGR2 are potential therapeutic targets in DTX resistance. No significant financial relationships to disclose.

scholarly journals MicroRNAs and Their Roles in Breast Cancer Bone Metastasis

2021 ◽  
Author(s):  
Margherita Puppo ◽  
Manoj K. Valluru ◽  
Philippe Clézardin
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Regulate Gene Expression ◽  
Mrna Targets ◽  
Advanced Therapies ◽  
Advanced Stages ◽  
Breast Cancer Bone Metastasis

AbstractBone metastasis occurs in advanced stages of breast cancer, worsening the quality of life and increasing the mortality of patients. Current treatments for bone metastasis are only palliative, and efficient therapeutic targets need to be still identified. MicroRNAs (miRNAs) are a large class of small non-coding RNAs that regulate gene expression within cells. Interestingly, the expression of certain miRNAs has been associated with several stages of bone metastasis progression, highlighting the importance of these small RNAs during the course of the metastatic disease. In this review, we aim to summarise the most recent findings on miRNAs and their mRNA targets in driving breast cancer bone metastasis. Furthermore, we discuss the possibility to use miRNAs as direct therapeutic targets or as advanced therapies for breast cancer bone metastasis, as well as their potential as predictive biomarkers of bone metastasis for an early diagnosis and a better tailoring of therapies for cancer patients.

scholarly journals Genomic Landscape of Appendiceal Neoplasms

2018 ◽  
pp. 1-18 ◽  
Author(s):  
Celina S.-P. Ang ◽  
John Paul Shen ◽  
Camille J. Hardy-Abeloos ◽  
Justin K. Huang ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Clinical Laboratory ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Signet Ring Cell ◽  
Low Grade ◽  
Histologic Subtype ◽  
Mutation Status ◽  
Tp53 Mutations ◽  
Appendiceal Neoplasms

Purpose Appendiceal neoplasms are heterogeneous and are often treated with chemotherapy similarly to colorectal cancer (CRC). Genomic profiling was performed on 703 appendiceal cancer specimens to compare the mutation profiles of appendiceal subtypes to CRC and other cancers, with the ultimate aim to identify potential biomarkers and novel therapeutic targets. Methods Tumor specimens were submitted to a Clinical Laboratory Improvement Amendments–certified laboratory (Foundation Medicine, Cambridge, MA) for hybrid-capture–based sequencing of 3,769 exons from 315 cancer-related genes and 47 introns of 28 genes commonly rearranged in cancer. Interactions between genotype, histologic subtype, treatment, and overall survival (OS) were analyzed in a clinically annotated subset of 76 cases. Results There were five major histopathologic subtypes: mucinous adenocarcinomas (46%), adenocarcinomas (30%), goblet cell carcinoids (12%), pseudomyxoma peritonei (7.7%), and signet ring cell carcinomas (5.2%). KRAS (35% to 81%) and GNAS (8% to 72%) were the most frequent alterations in epithelial cancers; APC and TP53 mutations were significantly less frequent in appendiceal cancers relative to CRC. Low-grade and high-grade tumors were enriched for GNAS and TP53 mutations, respectively (both χ2 P < .001). GNAS and TP53 were mutually exclusive (Bonferroni corrected P < .001). Tumor grade and TP53 mutation status independently predicted OS. The mutation status of GNAS and TP53 strongly predicted OS (median, 37.1 months for TP53 mutant v 75.8 GNAS- TP53 wild type v 115.5 GNAS mutant; log-rank P = .0031) and performed as well as grade in risk stratifying patients. Conclusion Epithelial appendiceal cancers and goblet cell carcinoids show differences in KRAS and GNAS mutation frequencies and have mutation profiles distinct from CRC. This study highlights the benefit of performing molecular profiling on rare tumors to identify prognostic and predictive biomarkers and new therapeutic targets.

scholarly journals Comprehensive RNA Sequencing in Adenoma-Cancer Transition Identified Predictive Biomarkers and Therapeutic Targets of Human CRC

2020 ◽  
Vol 20 ◽  
pp. 25-33 ◽  
Author(s):  
Mingzhe Zhu ◽  
Yanqi Dang ◽  
Zhenhua Yang ◽  
Yang Liu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Therapeutic Targets ◽  
Predictive Biomarkers

scholarly journals Long Non-Coding RNAs in Gliomas: From Molecular Pathology to Diagnostic Biomarkers and Therapeutic Targets

2018 ◽  
Vol 19 (9) ◽  
pp. 2754 ◽  
Author(s):  
Marek Vecera ◽  
Jiri Sana ◽  
Radim Lipina ◽  
Martin Smrcka ◽  
Ondrej Slaby
Keyword(s):  
Molecular Pathology ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Options ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Predictive Biomarkers ◽  
Biological Behavior ◽  
Diagnostic Biomarkers ◽  
Non Coding Rnas

Gliomas are the most common malignancies of the central nervous system. Because of tumor localization and the biological behavior of tumor cells, gliomas are characterized by very poor prognosis. Despite significant efforts that have gone into glioma research in recent years, the therapeutic efficacy of available treatment options is still limited, and only a few clinically usable diagnostic biomarkers are available. More and more studies suggest non-coding RNAs to be promising diagnostic biomarkers and therapeutic targets in many cancers, including gliomas. One of the largest groups of these molecules is long non-coding RNAs (lncRNAs). LncRNAs show promising potential because of their unique tissue expression patterns and regulatory functions in cancer cells. Understanding the role of lncRNAs in gliomas may lead to discovery of the novel molecular mechanisms behind glioma biological features. It may also enable development of new solutions to overcome the greatest obstacles in therapy of glioma patients. In this review, we summarize the current knowledge about lncRNAs and their involvement in the molecular pathology of gliomas. A conclusion follows that these RNAs show great potential to serve as powerful diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets.

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