ctDNA

Circulating tumor DNA (ctDNA) detection has been acknowledged as a promising liquid biopsy approach for cancer diagnosis, with various ctDNA assays used for early detection and treatment monitoring. Dispersible magnetic nanoparticle-based electrochemical detection methods have been proposed as promising candidates for ctDNA detection based on the detection performance and features of the platform material. This study proposes a nanoparticle surface-localized genetic amplification approach by integrating Fe3 O4 -Au core-shell nanoparticles into polymerase chain reactions (PCR)...

Circulating tumor DNA (ctDNA) holds promise as a biomarker for predicting clinical responses to therapy in solid tumors, and multiple ctDNA assays are in development. However, the heterogeneity in ctDNA levels prior to treatment (baseline) across different cancer types and stages and across ctDNA assays has not been widely studied. Friends of Cancer Research formed a collaboration across multiple commercial ctDNA assay developers to assess baseline ctDNA levels across five cancer types in early- and late-stage disease...

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, distant tumor recurrence remains a concern, prompting the exploration of total neoadjuvant therapy (TNT) as a comprehensive treatment strategy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens...

PURPOSE: Tissue derived tumor mutation burden (TMB) of ≥10 mutations/Mb is a histology agnostic biomarker for the immune checkpoint inhibitor (ICI) pembrolizumab. However, the dataset on which this was validated lacked colorectal cancers (CRCs), and there is limited evidence for immunotherapy benefit in CRC using this threshold. PATIENTS AND METHODS: CO.26 was a randomized phase II study of 180 patients comparing durvalumab and tremelimumab (D+T, n=119 patients) versus best supportive care (BSC, n=61 patients)...

PURPOSE OF REVIEW: This review explores the role of circulating tumor (ct)DNA as a biomarker for clinical decision-making and monitoring purposes in metastatic gastrointestinal stromal tumor (GIST) patients. We discuss key insights from recent clinical trials and anticipate the future perspectives of ctDNA profiling within the clinical landscape of GIST. RECENT FINDINGS: The identification and molecular characterization of KIT/platelet-derived growth factor receptor alpha (PDGFRA) mutations from ctDNA in metastatic GIST is feasible and reliable...

PURPOSE: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. MATERIALS AND METHODS: 75 patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and pre-operative and post-operative day 7 blood samples were collected...

Uveal cancer (UM) offers a complex molecular landscape characterized by substantial heterogeneity, both on the genetic and epigenetic levels. This heterogeneity plays a critical position in shaping the behavior and response to therapy for this uncommon ocular malignancy. Targeted treatments with gene-specific therapeutic molecules may prove useful in overcoming radiation resistance, however, the diverse molecular makeups of UM call for a patient-specific approach in therapy procedures. We need to understand the intricate molecular landscape of UM to develop targeted treatments customized to each patient's specific genetic mutations...

PURPOSE: Conventional surveillance methods are poorly sensitive for monitoring appendiceal cancers (AC). This study investigated the utility of circulating tumor DNA (ctDNA) in evaluating systemic therapy response and recurrence after surgery for AC. METHODS: Patients from two specialized centers who underwent tumor-informed ctDNA testing (Signatera) were evaluated to determine the association between systemic therapy and ctDNA detection. In addition, the accuracy of ctDNA detection during surveillance for the diagnosis of recurrence after complete cytoreductive surgery (CRS) for grade 2-3 ACs with peritoneal metastases (PM) was investigated...

PURPOSE: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. METHODS: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes...

Circulating tumor DNA (ctDNA) is an auspicious tumor biomarker released into the bloodstream by tumor cells, offering abundant information concerning cancer genes. It plays a crucial role in the early diagnosis of cancer. However, due to extremely low levels in body fluids, achieving a simple, sensitive, and highly specific detection of ctDNA remains challenging. Here, we constructed a purification-free fluorescence biosensor based on quadratic amplification of ctDNA by combining nicking enzyme mediated amplification (NEMA) and catalytic hairpin assembly (CHA) reactions...

Emergence of acquired resistance limits the efficacy of the anti-EGFR therapies cetuximab and panitumumab in metastatic colorectal cancer. In the last decade, preclinical and clinical cohort studies have uncovered genomic alterations that confer a selective advantage to tumor cells under EGFR blockade, mainly downstream re-activation of RAS-MEK signaling and mutations in the extracellular domain of EGFR (EGFR-ECD). Liquid biopsies (genotyping of ctDNA) have been established as an excellent tool to easily monitor the dynamics of genomic alterations resistance in the blood of patients and to select patients for rechallenge with anti-EGFR therapies...

Small cell lung cancer (SCLC) is a highly aggressive type of cancer frequently diagnosed with metastatic spread, rendering it surgically unresectable for the majority of patients. Although initial responses to platinum-based therapies are often observed, SCLC invariably relapses within months, frequently developing drug-resistance ultimately contributing to short overall survival rates. Recently, SCLC research aimed to elucidate the dynamic changes in the genetic and epigenetic landscape. These have revealed distinct subtypes of SCLC, each characterized by unique molecular signatures...

BACKGROUND: Colorectal cancer (CRC) with the Raf murine sarcoma viral oncogene homolog B ( BRAF ) V600E had a relatively poor prognosis. Anaplastic lymphoma kinase ( ALK ) fusion and the mesenchymal-to-epithelial transition factor ( MET ) amplification have been recognized as potentially important therapeutic targets in non-small cell lung cancer (NSCLC). However, both of them are of extremely lower frequencies (<2%) in metastatic CRC, and few studies have mentioned the real application of their inhibitors in CRC treatment...

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled...

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus dose/schedule optimization requires extended follow-up to assess prolonged treatment effects. METHODS: Long-term safety/tolerability and antitumor efficacy of three camonsertib monotherapy dose levels/schedules were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on/4 off (160 3/4; the preliminary recommended phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on/1 off (160 3/4, 2/1w)...

Liquid biopsy has been investigated as a novel method to overcome the numerous challenges in gastric cancer (GC) management. This non-invasive, feasible, and easy-to-repeat method has been shown to be cost-effective and capable of increasing diagnostic sensitivity and prognostic assessment. Additionally, it is potentially accurate to aid decision-making and personalized treatment planning. MicroRNA (miRNA) and circulating tumor DNA (ctDNA) markers can enhance GC management in various aspects, including diagnosis (mainly earlier diagnosis and the ability to perform population-based screening), prognosis (more precise stratification of prognosis), and treatment (including more accurate prediction of treatment response and earlier detection of resistance to the treatment)...

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern-whether it's neoadjuvant, adjuvant, or a combination of both-is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices...

Classic Hodgkin lymphoma (cHL) treatment paradigms are undergoing a shift with the integration of immune checkpoint inhibitors (ICIs) into both first-line and relapsed/refractory (R/R) regimens. In first-line therapy, the synergy between ICIs and chemotherapy may surpass the previous standards of ABVD and BV-AVD established by landmark trials including RATHL and ECHELON-1. In R/R disease, the combination of ICIs with chemotherapy has begun to challenge the paradigm of chemotherapy as a bridge to consolidative autologous stem cell transplantation...

PURPOSE: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. MATERIALS AND METHODS: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA)...

PURPOSE: Minimal residual disease (MRD) detection identifies patients with colorectal adenocarcinoma (CRC) likely to recur following definitive treatment. We evaluated a plasma only MRD assay to predict recurrence and survival in metastatic CRC patients undergoing curative intent procedures (surgery and/or radiotherapy), with or without (neo)adjuvant chemotherapy. The primary objective of this study was to assess the correlation of post-procedure tumor cfDNA detection status with radiographic disease recurrence (RFS)...