European Urology: Quantitative and qualitative analysis of liquid biopsies to guide clinical decision-making in prostate cancer

Recent studies have provided insights into the molecular landscape of prostate cancer (PC), identifying prognosmical biomarkers, operational targets, and drug-resistant biomarkers.
difficulty in obtaining suitable tumor materials for molecular testing is one of the reasons hindering the clinical application of genomic mapping.
active tissue examination of primary prostate tumors is routine, but it is often insufficient in yield, and the fixed process affects DNA quality.
resistance to standard-treated androgen-targeted drugs (AR) usually involves multiclonal genomic changes, which may be related to the choice of follow-up treatment routes.
individual tumor biopsies, whether primary or metastasis lesions, have limited ability to capture spatial heterogeneity, especially for repeated longitudinal assessments.
, primary PC is one of the most spatially heterogeneous and cloning complex types of cancer.
of liquid biopsies includes the analysis of tumor substances present in body fluids.
this substance can be present in the form of biological molecules such as circulating tumor DNA (ctDNA), RNA, protein and mitochondrial DNA), circulating tumor cells (CTCs), or extracellular cystic follicles (EVs).
liquid biopsy has become an attractive way to study tumor molecular landscape in a minimally invasive way, allowing real-time snapshots of the entire tumor load.
addition, biomarkers based on liquid biopsies can serve as an early endpoint for clinical trials to accelerate drug development.
a new study published today in European Urology reviews current knowledge of blood-based liquid biopsy components, their impact on PC clinical decision-making, the opportunity to accelerate precision medicine, and the challenges of implementing such tests in clinical practice.
researchers conducted a systematic review of the PubMed/MEDLINE database to determine the literature published between 2005 and July 2020 on CTCs, ctDNA and EVs in PCs.
select articles involving CTCs, ctDNA, and EVs in the blood of PC patients and consider the literature cited there.
above describes the workflow of the pre-analysis, analysis, and post-analysis steps of the cfDNA study of the blood.
intravenous puncture, blood is collected using a test tube containing anticoagulants (EDTA and citric acid are superior to heparin).
time from sample collection to processing is critical because cfDNA degrades in a matter of hours.
to overcome this problem, test tubes containing different DNA stabilizers can be used; The use of these tubes is particularly relevant in large multi-center studies of centralized analysis, or in general, when samples are not processed at the collection point.
recommends a two-step centrifugation method to separate plasma components and extract cfDNA from the plasma.
if cfDNA is not extracted immediately, plasma can be stored for a longer period of time at 80 degrees C, although repeated freezing and thawing cycles can increase non-tumor DNA contamination, thereby impairing the quality of cfDNA.
cfDNA is isolated, quality control (QC) tests are performed prior to identification to assess cfDNA concentration and fragment size.
This review points out that the authors analyze how liquid biopsy techniques can be applied to the clinical treatment of PCs in four ways: quantitative prognostic and reactive biomarkers to accelerate drug development, clinical application of limited prostate cancer, liquid biopsies with precise use of AR-targeted agents, and predictive biomarkers for targeted therapy.
liquid biopsy can accelerate the development of biomarkers for accurate PC care.
As new biomarker-driven treatments are validated, liquid biopsies also represent an opportunity to promote the implementation of genomic testing in community practice, with metastasis biopsies carried out less in community practice than in academic centres.
value of CTC as a prognostic and reactive biomarker has been clearly demonstrated, providing an alternative biomarker for accelerating drug development and potentially guiding treatment decisions.
, however, the heterogeneity between cost and acquisition techniques, as well as research on CTC definition and separation platforms, complicates the conversion of CTC analysis to routine clinical trials.
studies have shown that ctDNA dynamics may also be a useful prognostic and reactive biomarker in clinical practice, although further clinical trial qualifications are needed.
Because both CTCs and ctDNA produce parallel tumor loads, their suitability in localized diseases can be challenging, although with the development of ultra-sensitive testing methods, liquid biopsies may have the potential to help monitor patients after treatment, or to supplement tissue-based biomarkers to improve patient stratization.
the use of EVs in clinical settings, which can complement CTC and ctDNA analysis, but challenges are challenged in standardizing isolation methods and downstream applications.
addition, the study of new features of liquid biopsy analysis, such as fragment histology (based on ctDNA fragment size), origin tissue analysis, and methylation analysis, may provide information for early tumor stages.
important, since liquid biopsies can reveal a wider range of mutations in a variety of adversos, integrating these complex multi-dimensional data into composite biomarkers is a current requirement and an active area of research in this field.
Overall, over the past decade, the PC's liquid living tissue examination field has made exponential progress, developing prognosmical and predictive biomarkers, and promising minimally invasive means of monitoring tumor evolution.
biopsy can guide treatment decisions and accelerate the development of PC precision medicine.
, however, issues that need to be addressed include standardization of sensitivity and specificity of assays, forward-looking clinical identification of different assays, and cost and accessability to support their implementation in conventional clinical practice.
: Irene Casanova-Salas, et al. Quantitative and Qualitative Analysis of Blood-based Liquid 4 Biopsies to Inform Clinical Decision-making in Prostate Cancer. European Urology January 06, 2021, DOI:MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mays Medical, are not authorized, and may not be reproduced by any media, website or individual, and shall be reproduced with the words "Source: Mays Medicine".
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