Cell free tumour DNA

The cumulative pool of cell-free DNA (cfDNA) molecules within bodily fluids represents a highly dense and multidimensional information repository. This "biological mirror" provides real-time insights into the composition, function, and dynamics of the diverse genomes within the body, enabling significant advancements in personalized molecular medicine. However, effective use of this information necessitates meticulous classification of distinct cfDNA subtypes with exceptional precision. While cfDNA molecules originating from different sources exhibit numerous genetic, epigenetic, and physico-chemical variations, they also share common features that complicate analyses...

BACKGROUND: Liquid biopsy is a minimally-invasive method of sampling bodily fluids, capable of revealing evidence of cancer. The distribution of cell-free DNA (cfDNA) fragment lengths has been shown to differ between healthy subjects and cancer patients, whereby the distributional shift correlates with the sample's tumour content. These fragmentomic data have not yet been utilised to directly quantify the proportion of tumour-derived cfDNA in a liquid biopsy. RESULTS: We used statistical learning to predict tumour content from Fourier and wavelet transforms of cfDNA length distributions in samples from 118 cancer patients...

Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence...

The clinical presentation of renal cell cancer (RCC) is shifting towards incidental and early detection, creating new challenges in RCC diagnosis. Overtreatment might be reduced with the development of new diagnostic biomarkers to distinguish benign from malignant small renal masses (SRMs). Differently from tissue biopsies, liquid biopsies are obtained from a patient's blood or urine and, therefore, are minimally invasive and suitable for longitudinal monitoring. The most promising types of liquid biopsy biomarkers for RCC diagnosis are circulating tumour cells, extracellular vesicles (EVs) and cell-free DNA...

PURPOSE: To map current literature and provide an overview of upcoming future diagnostic and prognostic methods for upper tract urothelial carcinoma (UTUC), including translational medical science. METHODS: A scoping review approach was applied to search the literature. Based on the published literature, and the experts own experience and opinions consensus was reached through discussions at the meeting Consultation on UTUC II in Stockholm, September 2022. RESULTS: The gene mutational profile of UTUC correlates with stage, grade, prognosis, and response to different therapeutic strategies...

BACKGROUND: Next-generation sequencing (NGS) of plasma cell-free DNA identifies driver mutations in advanced non-small cell lung cancer (NSCLC) and may complement routine molecular evaluation. The utility of liquid NGS at the start of tumour workup is undetermined. METHODS: This is a randomised study of patients with suspected advanced NSCLC. All patients received blood liquid NGS testing at their first clinic visit and underwent standard histological diagnosis and tissue genotyping, encompassing polymerase chain reaction based methods for EGFR mutation, immunohistochemical (IHC) staining for ALK fusion and BRAF V600E mutation, and an IHC screening followed by confirmation using fluorescence in situ hybridization confirmation for ROS1 fusion...

PURPOSE: The prognosis of upper urinary tract urothelial carcinoma (UTUC) is associated with tumour grade (G) and stage. Despite preoperative risk stratification and radical treatment, recurrence and progression are common. Thus, prognostic and monitoring biomarkers are needed. This feasibility study aimed to investigate if targeted analyses on circulating tumour DNA (ctDNA) in plasma could identify tumour-specific gene variants, and thus have potential for further evaluation as a biomarker in UTUC...

BACKGROUND: A rapid, low-cost blood test that can be applied to reliably detect multiple different cancer types would be transformational. METHODS: In this large-scale discovery study (n = 2092 patients) we applied the Dxcover® Cancer Liquid Biopsy to examine eight different cancers. The test uses Fourier transform infrared (FTIR) spectroscopy and machine-learning algorithms to detect cancer. RESULTS: Area under the receiver operating characteristic curve (ROC) values were calculated for eight cancer types versus symptomatic non-cancer controls: brain (0...

Chronic inflammation leads to many maladies in lung cancer. Tumor necrosis factor-alpha (T NF- α), a pleiotropic proinflammatory cytokine regulates the activation of the nuclear factor-κB (NF-κB) to drive many physiological and pathological signaling pathways in inflammation and cancer apoptosis. This study identified a novel natural product to inhibit T NF-α induced NF-κB activation. Virtual docking of ZINC natural product library and computational modeling analysis showed compounds that target crucial amino acid residues on p50 protein involved in DNA binding...

Background Glioblastoma (GBM) is the most common malignant primary brain tumour and confers a very poor prognosis. Maximal safe resection of tumour is the goal of neurosurgical intervention and may be more easily achieved through the use of surgical adjuncts such as fluorescence-guided surgery (FGS). 5-Aminolevulinic acid (5-ALA) accumulates in GBM tissue and fluoresce red, distinguishing tumour cells from the surrounding tissue and therefore making resection easier. 5-ALA-guided resection in GBM has been shown to increase resection rates and prolong progression-free survival without impacting post-operative morbidity...

Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples)...

BACKGROUND: Ovarian cancer affects the cells of the ovaries, and epithelial cancer is the most common type of malignant ovarian cancer. The homologous recombination repair pathway enables error-free repair of DNA double-strand breaks. Damage of key genes associated with this pathway leads to homologous recombination deficiency (HRD), which results in unrepaired DNA and can lead to cancer. Tumours with HRD are believed to be sensitive to treatment with poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as niraparib...

The low distribution of hydrophobic anticancer drugs in patients is one of the biggest limitations during conventional chemotherapy. SDS-based polyelectrolyte multicore nanocarriers (NCs) prepared according to the layer by layer (LbL) procedure can release paclitaxel (PTX), and selectively kill cancer cells. Our main objective was to verify the antitumor properties of PTX-loaded NCs and to examine whether the drug encapsulated in these NCs retained its cytotoxic properties. The cytotoxicity of the prepared nanosystems was tested on MCF-7 and MDA-MB-231 tumour cells and the non-cancerous HMEC-1 cell line in vitro...

INTRODUCTION: Breast cancer (BC), a heterogeneous disease, is one of the leading causes of cancer-related deaths among women worldwide. Circulating cell-free DNA (cfDNA) levels have been persistently reported to be elevated in BC patients. In the current study, we evaluated the correlation between the cfDNA levels in patients with BC and its subtypes. METHODS: We recruited newly diagnosed, histopathologically confirmed BC patients aged >18 years (N=39), who did not have any previous malignancy, from the Department of Surgical Oncology, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India...

Precision radiotherapy refers to the ability to deliver radiation doses with sub-millimetre accuracy. It does not however consider individual variation in tumour or normal tissue response, failing to maximise tumour control and minimise toxicity. Combining precise delivery with personalised dosing, through analysis of cell-free DNA, would redefine precision in radiotherapy.

BACKGROUND: In breast cancer, as in all cancers, genetic and epigenetic deregulations can result in out-of-context expressions of a set of normally silent tissue-specific genes. The activation of some of these genes in various cancers empowers tumours cells with new properties and drives enhanced proliferation and metastatic activity, leading to a poor survival prognosis. RESULTS: In this work, we undertook an unprecedented systematic and unbiased analysis of out-of-context activations of a specific set of tissue-specific genes from testis, placenta and embryonic stem cells, not expressed in normal breast tissue as a source of novel prognostic biomarkers...

INTRODUCTION: In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers...

It is now well established that the biology of cancer is influenced by not only malignant cells but also other components of the tumour microenvironment. Chronic inflammation and fibrosis have long been postulated to be involved in carcinogenesis. Chronic inflammation can promote tumorigenesis via growth factor/cytokine-mediated cellular proliferation, apoptotic resistance, immunosuppression; and free-radical-induced oxidative deoxyribonucleic acid damage. Fibrosis could cause a perturbation in the dynamics of the tumour microenvironment, potentially damaging the genome surveillance machinery of normal epithelial cells...

BACKGROUND: It has been hypothesised that manipulation during surgery releases tumoral components into circulation. We investigate the effect of surgery on plasma-borne DNA biomarkers and the oncological outcomes in resectable pancreatic ductal adenocarcinoma (PDAC). We also compare non-touch isolation techniques (NTIT) with standard techniques. MATERIALS AND METHODS: We performed a systematic review and a meta-analysis of studies analysing liquid biopsy as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and messenger RNA (mRNA) in resectable PDAC patients who underwent surgery and its association with overall survival (OS) and disease-free survival (DFS)...

BACKGROUND: There is an unmet clinical need for accurate non-invasive tests to facilitate the early diagnosis of lung cancer. We propose a combined model of clinical, imaging, and cell-free DNA methylation biomarkers that aims to improve the classification of pulmonary nodules. METHODS: We conducted a prospective specimen collection and retrospective masked evaluation study. We recruited participants with a solitary pulmonary nodule sized 5-30 mm from 24 hospitals across 20 cities in China...