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Pan-Cancer Pre-Treatment ctDNA Detection Using a Highly Sensitive Tumor-Informed Assay.

Circulating tumor DNA (ctDNA) has many potential applications in the management of cancer, including detection, monitoring, and treatment response assessment. This study evaluates pre-treatment ctDNA detection in a single-institution pan-cancer cohort using a highly sensitive tumor-informed ctDNA assay. Participant samples were collected at the University Health Network across six study cohorts. A total of 273 patients with stage II-IV cancers spanning 16 tumor types were analyzed using a personalized tumor-informed assay (RaDaR®). Harmonized methods were employed to mitigate the impact of var…

A Dual-Channel Synergistic Ultrasensitive Biosensor for Tumor Liquid Biopsy.

Liquid biopsy technology, which detects circulating tumor DNA (ctDNA) in cerebrospinal fluid, plays a crucial role in the early diagnosis and precision treatment of gliomas. However, the intrinsically low abundance and rapid clearance of ctDNA pose substantial challenges for conventional analytical techniques, such as droplet digital PCR and next-generation sequencing. Here, we introduce a label-free dual-channel synergistic detection strategy that enables quantitative analysis of ctDNA at the zeptomolar level. Leveraging a synergistic design that includes structural symmetry breaking and mome…

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.9% specificity. Through an analysis of 171 patients with early-stage lung cancer from the TRACERx study, we detected ctDNA pre-operatively within 81% of patients with lung adenocarcinoma (LUAD), including 53% of those with patholo…

Whole-genome sequencing of cell-free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas.

The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor-agnostic approaches report ctDNA in 10-15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the proportion of patients with ctDNA, a sensitive tumor-informed strategy is preferred, as it ensures the detected signal originates from the adenoma. Here, tumor-informed whole-genome sequencing-based ctDNA analysis (MRD-EDGESNV) was applied to two independent cohorts. Cohort 1, comprising 93 patients with …

Detection of Tumor-Associated Membrane Receptors on Extracellular Vesicles from Non-Small Cell Lung Cancer Patients via Immuno-PCR.

Precision cancer medicine for non-small-cell lung cancer (NSCLC) has increased patient survival. Nevertheless, targeted agents towards tumor-associated membrane receptors only result in partial remission for a limited time, calling for approaches which allow longitudinal treatment monitoring. Rebiopsy of tumors in the lung is challenging, and metastatic lesions may have heterogeneous signaling. One way ahead is to use liquid biopsies such as circulating tumor DNA or small extracellular vesicles (sEVs) secreted by the tumor into blood or other body fluids. Herein, an immuno-PCR-based detection …

Longitudinal ultrasensitive ctDNA monitoring for high-resolution lung cancer risk prediction.

Biomarkers accurately informing prognostic assessment and therapeutic strategy are critical for improving patient outcome in oncology. Here, we apply a whole-genome, tumor-informed circulating tumor DNA (ctDNA) detection approach to address this challenge, leveraging 1,800 variants across 2,994 plasma samples from 431 patients with non-small cell lung cancer (NSCLC) from the TRACERx study. We show that ultrasensitive ctDNA detection below 80 parts per million both pre- and postoperatively is highly prognostic, and combinatorial analysis of the pre- and postoperative ctDNA status identifies an …

Molecular Testing in Breast Cancer: Current Status and Future Directions.

Molecular testing in breast cancer is a rapidly developing field that is becoming increasingly integral to patient care. This article provides an overview of currently available molecular assays and testing modalities that have prognostic, predictive, and therapeutic value. These include multigene assays for invasive breast cancer (Oncotype DX, MammaPrint, Prosigna, and Breast Cancer Index) and ductal carcinoma in situ (Oncotype DX DCIS and DCISionRT) and companion tests to detect PIK3CA mutations and NTRK fusions. The various assays related to immune checkpoint inhibitors, consisting of immun

Risk Stratification in Renal Cell Carcinoma: A Narrative Review.

Renal cell carcinoma (RCC) accounts for the majority of kidney cancers, with approximately 80,000 new diagnoses and over 14,000 deaths annua … limited by their reliance on clinical and pathologic variables alone. Emerging biomarkers-including circulating tumor DNA, methylated DNA, artificial intelligence-based radiomics, and tissue-based molecular signatures-show promise for improving risk discrimination. The molecular heterogeneity of RCC underscores an urgent need for integrated molecular-clinical-pathologi …

Liquid biopsy-guided kidney-sparing management in upper tract urothelial carcinoma: from preoperative risk stratification to perioperative surveillance.

Upper tract urothelial carcinoma (UTUC) presents a clinically important gap in urologic oncology: treatment intensity is determined before s … r, and protein assays, appear most mature for noninvasive detection and preoperative triage. Plasma circulating tumor DNA (ctDNA), in contrast, appears more closely linked to biological upstaging, occult muscle-invasive or non-organ-confined disease, perioperative risk refinement, and molecular residual disease surveillance. This review follows the KSS decision chain f …

[Value and controversy of prophylactic hyperthermic intraperitoneal chemotherapy in locally advanced colorectal cancer].

Locally advanced colorectal cancer patients are characterized by poor prognosis and high recurrence rates, with peritoneal metastasis rates … entification of high-risk factors are crucial for improving therapeutic outcomes, and tests such as circulating tumor DNA and free peritoneal cell DNA provide new avenues for early screening. The value of prophylactic HIPEC varies across different studies, and its complications and risks should not be overlooked. The selection of chemotherapy drugs, dosage, and persona …

Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.

Cancer manifestation is a multistep process involving accumulation of various genetic and epigenetic changes that results in oncogenic "hallmarks of cancer" processes including genomic instability. Exploitation of aberrant DNA-damage response (DDR) mechanisms in cancer is in part a goal of many therapeutic strategies, and recent evidence supports the role of targeting DDR in modulating the tumor immune microenvironment to enhance immunotherapeutic response. Improved cancer profiling, including next-generation and whole-genome mutational sequencing of tumor tissue, as well as circulating nuclei

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… BCSS: breast cancer specific survival; CBR: clinical benefit rate; ctDNA: circulating tumor DNA; DCR: disease control rate; DDR: DNA-damage response; DMFS: distant metastasis free survival; DOR: duration of response; gBRCA: germline BRCA; HRD: homologous recombination-deficiency; LRFS: locoregional relapse … AML: acute myeloid leukemia; CBR: clinical benefit rate; CPS: combined positive score (PD-L1 expression) CR: complete response; CTC: circulating tumor cells; ctDNA: circulating tumor DNA; DCR: disease control rate; DDR: DNA-damage response; DMFS: distant metastasis free survival; DOR: duration of response …

Combination of IL-34 and AFP improves the diagnostic value during the development of HBV related hepatocellular carcinoma.

IL-34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBV-HCC). Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV-HCC patients. Serum IL-34 and MCSF, or intrahepatic IL-34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined using ELISA or immunohistochemistry. Serum IL-34 was 1.7

pH-responsive neutrophil membrane camouflage Ga-Mn bimetallic nanodecoy triggers apoptosis-immunity-metastasis suppression for tumor therapy.

Mitochondria-mediated apoptosis and immunogenic cell death (ICD) are promising avenues in cancer therapy; however, they encounter challenges such as resistance to apoptosis and inadequate cytoplasmic sensing of mitochondrial DNA (mtDNA). Additionally, metastatic tumors remain challenging due to the lack of efficient systemic therapies that activate the immune system with low side effects. In this study, we introduce a pH-responsive neutrophil membrane camouflage nanoplatform (MGF@laN NPs) designed for the co-delivery of gallium (Ga3+) and manganese (Mn2+) ions, with the objective of orchestrat

Molecular filler-enhanced DNA nanomachines enable one-step multiplex quantification of ctDNA for mutation analysis and metastasis-associated assessment.

Detection of low-abundance biomarkers like circulating tumor DNA (ctDNA) remains challenging for molecular diagnosis and therapeutic management of cancer. Here, we developed a homogeneous electrochemical platform using metal ion-mediated DNA self-assembly enhanced by molecular fillers, enabling simultaneous, amplification-free, label-free, and enzyme-free detection of dual biomarkers. Incorporation of methylene blue into DNA nanostructures can suppress non-specific ion leakage, enhance sensitivity by 100-fold and signal-to-noise ratio by 2.5-fold. Target binding triggered DNA nanomachines disa…

Genome-wide methylome profiling of cell-free DNA enables prognostication of patients with castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with few biomarkers to inform treatment selection or patient prognosis. Methylation profiles of plasma circulating tumour DNA (ctDNA) accurately reflect tumour methylomes and may reveal novel biomarkers of mCRPC. METHODS: To establish a novel mCRPC-associated methylation signature for detection of ctDNA, we performed plasma methylome profiling on 27 mCRPC patients and 10 controls (cohort 1). Signature-based ctDNA detection was evaluated across prostate cancer (PC) disease stages using an internal coho

Investigation of a methylated BCAT1 and IKZF1 circulating tumour DNA blood test for monitoring treatment response in patients with colorectal cancer.

PURPOSE: Colorectal cancer (CRC) treatment failure results in high mortality. The current CRC treatment response monitoring blood biomarker carcinoembryonic antigen (CEA) lacks specificity. Methylated BCAT1/IKZF1 circulating tumour DNA (ctDNA) indicates CRC, but its utility during therapy is uncertain. This study examined whether during-treatment measurement of BCAT1/IKZF1 ctDNA reflects CRC treatment efficacy. METHODS: Plasma was collected from CRC patients before and during chemotherapy, targeted therapy and/or radiotherapy. Cell-free DNA was extracted, bisulphite-converted and assayed via

The relationship between circulating tumor biomarkers and prognosis of appendix cancer: A systematic review and meta-analysis.

BACKGROUND: The prognostic significance of circulating biomarkers in appendiceal neoplasms remains inconsistent across studies, hindering th … (CA125, CA19-9, CEA, Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), and circulating tumor DNA (ctDNA)) were included. CA125 demonstrated independent prognostic value for both OS (HR=2.46[1.78-3.38, 95 % CI]) and DFS/PFS (HR=1.72[1.14-2.59, 95 % CI]), while CA19-9 specifically predicted DFS/PFS deterioration (HR=2.69[2.01-3.61, 95 % CI]). CEA …

Differential expression and hypermethylation of apoptotic genes in circulating nucleic acids are associated with clinical phenotypes of prostate cancer and benign prostatic hyperplasia in Nigerians.

BACKGROUND: During carcinogenesis, cells have an increased ability to survive in the face of death-inducing mechanisms (apoptosis). Subversion of apoptosis is regarded as one of the primary factors helping the evolution of tumor cells. This study described the gene expression and DNA methylation of selected genes associated with apoptosis in prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: The study involved a total of 195 participants: 65 with prostate cancer, 65 with BPH, and 65 apparently healthy controls. Circulating DNA/RNA was extracted using Qiagen kits. RNA was r

Prospective Molecular Profiling of Circulating Tumor Cells from Patients with Melanoma Receiving Combinatorial Immunotherapy.

BACKGROUND: Blood molecular profiling of circulating tumor cells (CTCs) can enable monitoring of patients with metastatic melanoma during checkpoint inhibitor immunotherapy (CII) and in combination with targeted therapies. We developed a microfluidics-based CTC platform to explore CTC profiling utility in CII-treated patients with melanoma using a melanoma messenger RNA (mRNA)/DNA biomarker panel. METHODS: Blood samples (n = 213) were collected prospectively from 75 American Joint Committee on Cancer-staged III/IV melanoma patients during CII treatment and those enriched for CTCs. CTC profili

Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.

PURPOSE: Liquid biopsy monitoring in pediatric solid tumors is limited by low mutational burden and lack of trackable genomic drivers. We sought to develop a mutation-agnostic, methylation-based liquid biopsy framework enabling universal molecular surveillance of high-risk neuroblastoma. EXPERIMENTAL DESIGN: Using whole-genome Oxford Nanopore Technologies sequencing of high-risk neuroblastoma tumors, we compared tumor-derived methylation profiles with a comprehensive atlas of normal human cell types and identified 72 neuroblastoma-specific differentially methylated regions (meNBL) that were r