J Liq Biopsy. 2024 Feb 11;4:100146. doi: 10.1016/j.jlb.2024.100146. eCollection 2024 Jun.

ABSTRACT

As precision oncology has become a major part of the treatment landscape in oncology, liquid biopsies have developed as a particularly powerful tool as it surmounts several limitations of traditional tissue biopsies. These biopsies involve most commonly the isolation of circulating extracellular nucleic acids, including cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), as well as circulating tumor cells (CTCs), typically from blood. The clinical applications of liquid biopsies are diverse, encompassing the initial diagnosis and cancer detection, the application as a tool for prognostication in early and advanced tumor settings, the identification of potentially actionable alterations, the monitoring of response and resistance under systemic therapy and the detection of resistance mechanisms, the differentiation of distinct immune checkpoint blockade response patterns through serial samples, the prediction of immune checkpoint blockade responses based on initial liquid biopsy characteristics and the assessment of tumor heterogeneity. Moreover, molecular relapse monitoring in early-stage cancers and the personalization of adjuvant or additive therapy via MRD have become a major field of research in recent years. Compared to tissue biopsies, liquid biopsies are less invasive and can be collected serially, offering real-time molecular insights. Furthermore, liquid biopsies may allow for a more holistic evaluation of a patient's disease, as they assess material from all tumor sites and can theoretically reflect tumor heterogeneity. Furthermore, quicker turnaround-time also constitutes an advantage of liquid biopsies. Disadvantages or hurdles include the challenge of detecting low amounts of tumor deposits in peripheral blood or other fluids and the potential of different amounts tumor-shedding from different metastatic sites, as well as potentially false-positive from clonal hematopoietic mutations of indeterminate potential (CHIP) mutations. The clinical utility of liquid biopsies still must be validated in most settings and further research has to be done. Clinal trials including alternate bodily fluids and leveraging AI-technology are expected to revolutionize the field of liquid biopsies.

PMID:40027149 | PMC:PMC11863819 | DOI:10.1016/j.jlb.2024.100146

J Liq Biopsy. 2024 Feb 10;4:100145. doi: 10.1016/j.jlb.2024.100145. eCollection 2024 Jun.

ABSTRACT

Blood-based biomarkers investigation does not require invasive tissue biopsies and may explore diverse tumoral components such as proteins, microRNAs, circulating tumor cells, ctDNA, and exosomes and may better reflect tumor molecular heterogeneity, either temporal or spatial. ctDNA is related to tumor burden and represents a more objective measure of the total body disease burden than imaging findings. ctDNA profiling can be therefore useful to determine minimal residual disease (MRD), which is defined as the remaining tumor cells or tumor-derived material after definitive treatment in patients with no clinical evidence of disease. The detection of MRD is highly predictive of future disease recurrence. Although detectable MRD is associated with a poor prognosis, it is not clear whether MRD detection can guide therapy escalation to improve patient outcomes. In this review, we present four cases of epidermal growth factor receptor (EGFR) mutant NSCLC patients who received standard of care curative treatment and periodic radiological assessment and liquid biopsy analyses were carried out as follow-up. A tumor-informed 52 genes Oncomine Pan-Cancer Cell-Free assay (Thermo Fisher Scientific, Waltham, MA, USA), was used to identify single-nucleotide variants (SNVs), indels, copy number variations (CNVs), and RNA fusions in blood based liquid biopsy ctDNA in three of four patients. In one patient the approach used was through Commercial Kit Cobas EGFR Mutation Test v2 CE-IVD (Roche Diagnostics SL) that identifies 42 mutations in the EGFR gene. In one patient, an actionable oncogene driver alteration was identified in the ctDNA analysis, four months after radical intent concurrent chemoradiotherapy and six weeks before radiological distant relapse was clearly confirmed. There is no evidence of ctDNA or radiological disease relapse in the other three patients. Finally, a review of the literature addressing the potential value of MRD detection in this clinical setting is presented and discussed as well.

PMID:40027142 | PMC:PMC11863883 | DOI:10.1016/j.jlb.2024.100145

bioRxiv [Preprint]. 2025 Feb 17:2025.02.13.637721. doi: 10.1101/2025.02.13.637721.

ABSTRACT

Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here we performed single nucleus multiomics and spatial transcriptomics in up to 32 non-diabetic (ND), autoantibody-positive (AAB+), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine sub-types. Beta, acinar, and other cell types, and related cellular niches, had altered abundance and gene activity in T1D progression, including distinct pathways altered in AAB+ compared to T1D. We identified epigenomic drivers of gene activity in T1D and AAB+ which, combined with genetic association, revealed causal pathways of T1D risk including antigen presentation in beta cells. Finally, single cell and spatial profiles together revealed widespread changes in cell-cell signaling in T1D including signals affecting beta cell regulation. Overall, these results revealed drivers of T1D progression in the pancreas, which form the basis for therapeutic targets for disease prevention.

PMID:40027657 | PMC:PMC11870426 | DOI:10.1101/2025.02.13.637721