scholarly journals New Development of Biomarkers for Gastrointestinal Cancers: From Neoplastic Cells to Tumor Microenvironment

Biomedicines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 87 ◽  
Author(s):  
Jiajia Zhang ◽  
Shafat Quadri ◽  
Christopher Wolfgang ◽  
Lei Zheng
Keyword(s):  
Tumor Microenvironment ◽  
Rational Design ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Gastrointestinal Malignancies ◽  
Immune Biomarkers ◽  
New Development ◽  
Selection For ◽  
Monitor Treatment Response ◽  
Tumor Genome

Biomarkers refer to a plethora of biological characteristics that can be quantified to facilitate cancer diagnosis, forecast the prognosis of disease, and predict a response to treatment. The identification of objective biomarkers is among the most crucial steps in the realization of individualized cancer care. Several tumor biomarkers for gastrointestinal malignancies have been applied in the clinical setting to help differentiate between cancer and other conditions, facilitate patient selection for targeted therapies, and to monitor treatment response and recurrence. With the coming of the immunotherapy age, the need for a new development of biomarkers that are indicative of the immune response to tumors are unprecedentedly urgent. Biomarkers from the tumor microenvironment, tumor genome, and signatures from liquid biopsies have been explored, but the majority have shown a limited prognostic or predictive value as single biomarkers. Nevertheless, use of multiplex biomarkers has the potential to provide a significantly increased diagnostic accuracy compared to traditional single biomarker. A comprehensive analysis of immune-biomarkers is needed to reveal the dynamic and multifaceted anti-tumor immunity and thus imply for the rational design of assays and combinational strategies.

scholarly journals Molecular and Circulating Biomarkers of Brain Tumors

2021 ◽  
Vol 22 (13) ◽  
pp. 7039
Author(s):  
Wojciech Jelski ◽  
Barbara Mroczko
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Methylguanine Dna Methyltransferase ◽  
The Central Nervous System

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations.While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.

scholarly journals Recent Advances in the Discovery of Biomarkers for Canine Osteosarcoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Anita K. Luu ◽  
Geoffrey A. Wood ◽  
Alicia M. Viloria-Petit
Keyword(s):  
Clinical Practice ◽  
Standard Treatment ◽  
Predictive Biomarkers ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Future Directions ◽  
Diagnostic Biomarkers ◽  
Canine Osteosarcoma ◽  
The Past ◽  
Biomarker Research

Canine osteosarcoma (OSA) is an aggressive malignancy that frequently metastasizes to the lung and bone. Not only has there been essentially no improvement in therapeutic outcome over the past 3 decades, but there is also a lack of reliable biomarkers in clinical practice. This makes it difficult to discriminate which patients will most benefit from the standard treatment of amputation and adjuvant chemotherapy. The development of reliable diagnostic biomarkers could aid in the clinical diagnosis of primary OSA and metastasis; while prognostic, and predictive biomarkers could allow clinicians to stratify patients to predict response to treatment and outcome. This review summarizes biomarkers that have been explored in canine OSA to date. The focus is on molecular biomarkers identified in tumor samples as well as emerging biomarkers that have been identified in blood-based (liquid) biopsies, including circulating tumor cells, microRNAs, and extracellular vesicles. Lastly, we propose future directions in biomarker research to ensure they can be incorporated into a clinical setting.

Next-generation sequencing for tumor mutation quantification using liquid biopsies

2020 ◽  
Vol 58 (2) ◽  
pp. 306-313 ◽  
Author(s):  
Mariano Provencio ◽  
Clara Pérez-Barrios ◽  
Miguel Barquin ◽  
Virginia Calvo ◽  
Fabio Franco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Correlation Coefficient ◽  
Resistance Mutation ◽  
Response To Treatment ◽  
Clinical Samples ◽  
Next Generation ◽  
Liquid Biopsies ◽  
Nsclc Patients ◽  
Generation Sequencing

AbstractBackgroundNon-small cell lung cancer (NSCLC) patients benefit from targeted therapies both in first- and second-line treatment. Nevertheless, molecular profiling of lung cancer tumors after first disease progression is seldom performed. The analysis of circulating tumor DNA (ctDNA) enables not only non-invasive biomarker testing but also monitoring tumor response to treatment. Digital PCR (dPCR), although a robust approach, only enables the analysis of a limited number of mutations. Next-generation sequencing (NGS), on the other hand, enables the analysis of significantly greater numbers of mutations.MethodsA total of 54 circulating free DNA (cfDNA) samples from 52 NSCLC patients and two healthy donors were analyzed by NGS using the Oncomine™ Lung cfDNA Assay kit and dPCR.ResultsLin’s concordance correlation coefficient and Pearson’s correlation coefficient between mutant allele frequencies (MAFs) assessed by NGS and dPCR revealed a positive and linear relationship between the two data sets (ρc = 0.986; 95% confidence interval [CI] = 0.975–0.991; r = 0.987; p < 0.0001, respectively), indicating an excellent concordance between both measurements. Similarly, the agreement between NGS and dPCR for the detection of the resistance mutation p.T790M was almost perfect (K = 0.81; 95% CI = 0.62–0.99), with an excellent correlation in terms of MAFs (ρc = 0.991; 95% CI = 0.981–0.992 and Pearson’s r = 0.998; p < 0.0001). Importantly, cfDNA sequencing was successful using as low as 10 ng cfDNA input.ConclusionsMAFs assessed by NGS were highly correlated with MAFs assessed by dPCR, demonstrating that NGS is a robust technique for ctDNA quantification using clinical samples, thereby allowing for dynamic genomic surveillance in the era of precision medicine.

scholarly journals LKB1 and Tumor Metabolism: The Interplay of Immune and Angiogenic Microenvironment in Lung Cancer

2019 ◽  
Vol 20 (8) ◽  
pp. 1874 ◽  
Author(s):  
Laura Bonanno ◽  
Elisabetta Zulato ◽  
Alberto Pavan ◽  
Ilaria Attili ◽  
Giulia Pasello ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Redox Homeostasis ◽  
Suppressor Gene ◽  
Response To Treatment ◽  
Primary Resistance ◽  
Potential Applications ◽  
Liver Kinase B1 ◽  
Immunosuppressive Microenvironment ◽  
Tumor Types

Liver kinase B1 (LKB1) is a tumor suppressor gene whose inactivation is frequent in different tumor types, especially in lung adenocarcinoma (about 30% of cases). LKB1 has an essential role in the control of cellular redox homeostasis by regulating ROS production and detoxification. Loss of LKB1 makes the tumor cell more sensitive to oxidative stress and consequently to stress-inducing treatments, such as chemotherapy and radiotherapy. LKB1 loss triggers complex changes in tumor microenvironment, supporting a role in the regulation of angiogenesis and suggesting a potential role in the response to anti-angiogenic treatment. On the other hand, LKB1 deficiency can promote an immunosuppressive microenvironment and may be involved in primary resistance to anti-PD-1/anti-PD-L1, as it has been reported in lung cancer. The aim of this review is to discuss interactions of LKB1 with the tumor microenvironment and the potential applications of this knowledge in predicting response to treatment in lung cancer.

scholarly journals ERK1/2 signaling regulates the immune microenvironment and macrophage recruitment in glioblastoma

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Claire Lailler ◽  
Christophe Louandre ◽  
Mony Chenda Morisse ◽  
Thomas Lhossein ◽  
Corinne Godin ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Recent Observation ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Mrna Levels ◽  
Rna Seq ◽  
Immune Microenvironment ◽  
Oncogenic Signaling ◽  
Cancer Genome Atlas ◽  
Human Gbm

Abstract The tumor microenvironment is an important determinant of glioblastoma (GBM) progression and response to treatment. How oncogenic signaling in GBM cells modulates the composition of the tumor microenvironment and its activation is unclear. We aimed to explore the potential local immunoregulatory function of ERK1/2 signaling in GBM. Using proteomic and transcriptomic data (RNA seq) available for GBM tumors from The Cancer Genome Atlas (TCGA), we show that GBM with high levels of phosphorylated ERK1/2 have increased infiltration of tumor-associated macrophages (TAM) with a non-inflammatory M2 polarization. Using three human GBM cell lines in culture, we confirmed the existence of ERK1/2-dependent regulation of the production of the macrophage chemoattractant CCL2/MCP1. In contrast with this positive regulation of TAM recruitment, we found no evidence of a direct effect of ERK1/2 signaling on two other important aspects of TAM regulation by GBM cells: (1) the expression of the immune checkpoint ligands PD-L1 and PD-L2, expressed at high mRNA levels in GBM compared with other solid tumors; (2) the production of the tumor metabolite lactate recently reported to dampen tumor immunity by interacting with the receptor GPR65 present on the surface of TAM. Taken together, our observations suggest that ERK1/2 signaling regulates the recruitment of TAM in the GBM microenvironment. These findings highlight some potentially important particularities of the immune microenvironment in GBM and could provide an explanation for the recent observation that GBM with activated ERK1/2 signaling may respond better to anti-PD1 therapeutics.

scholarly journals Targeting extracellular and juxtamembrane FGFR2 mutations in chemotherapy-refractory cholangiocarcinoma

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Michael Bitzer ◽  
Stephan Spahn ◽  
Sepideh Babaei ◽  
Marius Horger ◽  
Stephan Singer ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Response To Treatment ◽  
Gene Fusions ◽  
Potential Treatment ◽  
Promising Candidate ◽  
Recommended Treatment ◽  
Tumor Boards ◽  
Functional Consequences ◽  
Selection For ◽  
A Current

AbstractIntrahepatic cholangiocarcinoma (iCCA) has emerged as a promising candidate for precision medicine, especially in the case of activating FGFR2 gene fusions. In addition to fusions, a considerable fraction of iCCA patients reveals FGFR2 mutations, which might lead to uncontrolled activation of the FGFR2 pathway but are mostly of unknown functional significance. A current challenge for molecular tumor boards (MTB) is to predict the functional consequences of such FGFR2 alterations to guide potential treatment decisions. We report two iCCA patients with extracellular and juxtamembrane FGFR2 mutations. After in silico investigation of the alterations and identification of activated FGFR2 downstream targets in tumor specimens by immunohistochemistry and transcriptome analysis, the MTB recommended treatment with an FGFR-inhibiting tyrosine kinase inhibitor. Both patients developed a rapidly detectable and prolonged partial response to treatment. These two cases suggest an approach to characterize further detected FGFR2 mutations in iCCA to enable patients´ selection for a successful application of the FGFR -inhibiting drugs.

SimBioSys TumorScope: Spatio-temporal modeling of the tumor microenvironment to predict chemotherapeutic response.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12650-e12650
Author(s):  
John A Cole ◽  
Joseph R Peterson ◽  
Tyler M Earnest ◽  
Micahel J Hallock ◽  
John R Pfeiffer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
3D Model ◽  
Healthcare Providers ◽  
Standard Of Care ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Temporal Modeling ◽  
Early Results ◽  
Spatio Temporal

e12650 Background: One of the most important sources of variability affecting each patient’s response to neoadjuvant chemotherapy (NACT) is drug and nutrient perfusion, The SimBioSys TumorScope is a computational decision-support system that is designed to predict the flow of drugs and nutrients throughout the tumor microenvironment, and the subsequent response of the tumor to treatment. By enabling healthcare providers to simulate a range of different standard-of-care treatment regimens in a realistic 3D model of each patient’s tumor, providers can predict which treatments are most effective, and provide the best possible care for their patients. Methods: SimBioSys TumorScope implements a multi-scale simulation technology that couples several biophysical and biochemical models in order to predict how individual patients' tumors respond to NACT. The simulations explicitly track the 3D morphology of the tumor and surrounding tissues (based on MRI images), as well as the concentrations of key nutrients and drugs as they change over time. At each location within the 3D model, these concentrations are used to predict cell growth and death rates. As different regions of the tumor grow or die, its macroscopic shape changes. Results: SimBioSys TumorScope was retrospectively applied to over 300 breast cancer patients that received NACT. Simulations were initialized with pre-treatment MRI data, and run through the entirety of each patient's specified treatment regimen. Predicted changes in tumor volume and longest dimension were then compared against measured values at several time-points after initiation of therapy, yielding Pearson correlations of over 0.93 for both. Work is underway to extend the technology to lung tumors; early results show very different metabolic behaviors from those of breast tumors, and significantly less response to treatment overall. Conclusions: Through accurate spatio-temporal modeling of drug and nutrient perfusion, metabolic behavior, and the physico-chemical interactions that arise between tissues, the SimBioSys TumorScope for Breast Cancer can accurately predict the response of patients treated with NACT.

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