Functional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma.

Purpose: The abundance and biological contribution of cancer-associated fibroblasts (CAF) in glioblastoma (GBM) are poorly understood. Here, we aim to uncover its molecular signature, cellular roles, and potential tumorigenesis implications.

Experimental Design: We first applied single-cell RNA sequencing (RNA-seq) and bioinformatics analysis to identify and characterize stromal cells with CAF transcriptomic features in human GBM tumors.

Short-term biological variation of serum tryptase.

Objectives: Serum tryptase is a biomarker of mast cell activation. Among others, it is used in the diagnosis of anaphylaxis where a significant increase during the acute phase supports the diagnosis. When evaluating changes in biomarker levels, it is of utmost importance to consider the biological variation of the marker.

Short-term biological variation of plasma uracil in a Caucasian healthy population.

Objectives: Plasma uracil is a new biomarker to assess the activity of dihydropyrimidine dehydrogenase before cancer treatment with fluoropyrimidine drugs. Knowledge on the biological variation of plasma uracil is important to assess the applicability of plasma uracil as a biomarker of drug tolerance and efficacy.

Methods: A total of 33 apparently healthy individuals were submitted to sequential blood draws for three days.

Short-term biological variation of serum glial fibrillary acidic protein.

Objectives: Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker for intracerebral diseases and is approved for clinical use in traumatic brain injury. GFAP is also being investigated for several other applications, where the GFAP changes are not always outstanding. It is thus essential for the interpretation of GFAP to distinguish clinical relevant changes from natural occurring biological variation.

Biological variation of serum neurofilament light chain.

Objectives: The neurofilament light chain (NfL) has emerged as a versatile biomarker for CNS-diseases and is approaching clinical use. The observed changes in NfL levels are frequently of limited magnitude and in order to make clinical decisions based on NfL measurements, it is essential that biological variation is not confused with clinically relevant changes. The present study was designed to evaluate the biological variation of serum NfL.

Inflammatory Cytokines and ctDNA Are Biomarkers for Progression in Advanced-Stage Melanoma Patients Receiving Checkpoint Inhibitors.

Purpose: Checkpoint inhibitors have significantly improved treatment of metastatic melanoma. However, 40-60% of patients do not respond to therapy, emphasizing the need for better predictive biomarkers for treatment response to immune checkpoint inhibitors. Prorammed death-ligand 1(PD-L1) expression in tumor cells is currently used as a predictive biomarker; however, it lacks specificity.

Genomic Profiling of Circulating Tumor DNA Predicts Outcome and Demonstrates Tumor Evolution in ALK-Positive Non-Small Cell Lung Cancer Patients.

With the rapid development of targeted therapies for the treatment of cancer, methods for predicting response and outcome are in high demand. Non-small cell lung cancer driven by genomic rearrangements of the anaplastic lymphoma kinase () gene can be successfully treated with ALK-targeted therapy. Unfortunately, a subset of patients does not respond, and all patients ultimately acquire resistance, highlighting the need for better clinical tools to manage these patients.

Day-to-day and within-day biological variation of cell-free DNA.

Background: Numerous studies have shown that cell-free DNA (cfDNA) levels may serve as a non-invasive biomarker of a broad spectrum of acute and chronic pathologies. However, in order to make clinical decisions based on cfDNA measurements, it is essential to understand the magnitude of biological variation so this variation is not confused with a variation that actually represent a clinically relevant change. The present study was designed to evaluate the biological variation of cfDNA in healthy subjects and lung cancer patients.

A method for treatment monitoring using circulating tumour DNA in cancer patients without targetable mutations.

Background: The potentials of circulating tumour DNA (ctDNA) have been studied for non-invasive disease monitoring in patients with targetable mutations. However, the majority of cancer patients harbour no targetable mutations. A workflow including targeted next-generation sequencing (NGS) and droplet digital PCR (ddPCR) could be used for monitoring treatment in these patients.

The T790M resistance mutation in EGFR is only found in cfDNA from erlotinib-treated NSCLC patients that harbored an activating EGFR mutation before treatment.

Background: Lung cancer patients with an activating mutation in the EGFR (epidermal growth factor receptor) can develop resistance to erlotinib treatment, which is often mediated by the T790M resistance mutation in EGFR. The difficulties in obtaining biopsies at progression make it challenging to investigate the appearance of the T790M mutation at progression in large patient cohorts. We have used cell free DNA (cfDNA) from patients treated with erlotinib to investigate if the development of a T790M mutation coincides with the presence of an activating EGFR mutation in the pre-treatment blood sample.

Increased PD-L1 expression in erlotinib-resistant NSCLC cells with gene amplification is reversed upon MET-TKI treatment.

Introduction: Cancer cells can achieve immune evasion by expressing the programmed death receptor 1 ligand (PD-L1) on the cell surface. Blockade of the receptor (PD-1) can avert this evasion. Here we aim at investigating PD-L1 expression in erlotinib-resistant lung cancer cells with () gene amplification.

Correlation between circulating mutant DNA and metabolic tumour burden in advanced non-small cell lung cancer patients.

Background: Mutated circulating cell-free DNA (cfDNA) has been suggested as a surrogate marker of tumour burden and aggressiveness of disease. We examined the association between the level of plasma mutant cfDNA and metabolic tumour burden (MTB) measured by F-fluoro-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT). Furthermore, the presence of mutant cfDNA was correlated with patient survival.

IGF1R depletion facilitates MET-amplification as mechanism of acquired resistance to erlotinib in HCC827 NSCLC cells.

EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2 years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance mechanisms have been identified including secondary EGFR-mutations, MET-amplification, and epithelial-mesenchymal transition (EMT). Previous studies have indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired resistance to EGFR-directed drugs as well as in EMT.