Circulating Cell-Free DNA—Diagnostic and Prognostic Applications in Personalized Cancer Therapy

Abstract: Genomic analyses in oncologic care allow for the development of more precise clinical laboratory tests that will be critical for personalized pharmacotherapy. Traditional biopsy-based approaches are limited by the availability of sequential tissue specimens to detect resistance. Blood-based genomic profiling (“liquid biopsy”) is useful for longitudinal monitoring of tumor genomes and can complement biopsies. Tumor-associated mutations can be identified in cell-free tumor DNA (ctDNA) from patient blood samples and used for monitoring disease activity. The US Food and Drug Administration approved a liquid biopsy test for EGFR-activating mutations in patients with non–small-cell lung cancer as a companion diagnostic for therapy selection. ctDNA also allows for the identification of mutations selected by treatment such as EGFR T790M in non–small-cell lung cancer. ctDNA can also detect mutations such as KRAS G12V in colorectal cancer and BRAF V600E/V600K in melanoma. Chromosomal aberration pattern analysis by low-coverage whole genome sequencing is a new, broader approach. Genomic imbalances detected in cell-free DNA (cfDNA) can be used to compute a copy number instability (CNI) score. In clinical studies, it was demonstrated that the change in CNI score can serve as an early predictor of therapeutic response to chemotherapy/immunotherapy of many cancer types. In multivariable models, it could be shown that the CNI score was superior to clinical...
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Review Articles: Focus on Pharmacodynamic Drug Monitoring Source Type: research

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Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Personalized Dendritic Cell Vaccines—Recent Breakthroughs and Encouraging Clinical Results Beatris Mastelic-Gavillet, Klara Balint, Caroline Boudousquie, Philippe O. Gannon and Lana E. Kandalaft* Department of Oncology, Center for Experimental Therapeutics, Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
CONCLUSIONS: With respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer. PMID: 30673873 [PubMed - as supplied by publisher]
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
CONCLUSIONS: With respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer. PMID: 30673872 [PubMed - as supplied by publisher]
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
ConclusionsWith respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Abstract Although rare, cutaneous metastases portend a poor prognosis and are often an indicator of widespread disease. Breast cancer and melanoma are the most common types of cancer that are associated with spread to and within the skin; however, other malignancies, such as lung, colon, head and neck, and hematologic, have been described with a degree of relative frequency. A variety of clinical appearances and syndromes of cutaneous metastases are presented and described in this article. Possible treatment options, including skin-directed therapies and immunotherapies, are also discussed. PMID: 30497674 [PubMed - in process]
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: Hematol Oncol Clin North Am Source Type: research
Conclusions. APAVAC is a simple method for AV with high clinical impact in very bad situations. It could be used in combination with other therapy and for residual disease control. Further clinical studies are planned in solid C as well as in HM.DisclosuresRouquet: URODELIA: Employment. Frayssinet: URODELIA: Employment.
Source: Blood - Category: Hematology Authors: Tags: 703. Adoptive Immunotherapy Source Type: research
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