Improving Cancer Detection and Treatment with Liquid Biopsies and ptDNA.
Ontology highlight
ABSTRACT:
SUBMITTER: Kessler MD
PROVIDER: S-EPMC6116552 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Improving Cancer Detection and Treatment with Liquid Biopsies and ptDNA.
Kessler Michael D MD Pawar Nisha R NR Martin Stuart S SS Antalis Toni M TM O'Connor Timothy D TD
Trends in cancer 20180801 9
Liquid biopsy, or the capacity to noninvasively isolate and analyze plasma tumor DNA (ptDNA) using blood samples, represents an important tool for modern oncology that enables increasingly safe, personalized, and robust cancer diagnosis and treatment. Here, we review advances in the development and implementation of liquid biopsy approaches, and we focus on the capacity of liquid biopsy to noninvasively detect oncological disease and enhance early detection strategies. In addition to noting the ...[more]
Similar Datasets
Project description:Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. Despite recent improvements in treatment and prevention, most of the current therapeutic options are weighted by side effects impacting patients' quality of life. Better patient selection towards systemic treatments represents an unmet clinical need. The recent multidisciplinary and molecular advancements in the treatment of CRC patients demand the identification of efficient biomarkers allowing to personalise patient care. Currently, core tumour biopsy specimens represent the gold-standard biological tissue to identify such biomarkers. However, technical feasibility, tumour heterogeneity and cancer evolution are major limitations of this single-snapshot approach. Genotyping circulating tumour DNA (ctDNA) has been addressed as potentially overcoming such limitations. Indeed, ctDNA has been retrospectively demonstrated capable of identifying minimal residual disease post-surgery and post-adjuvant treatment, as well as spotting druggable molecular alterations for tailoring treatments in metastatic disease. In this review, we summarise the available evidence on ctDNA applicability in CRC. Then, we review ongoing clinical trials assessing how liquid biopsy can be used interventionally to guide therapeutic choice in localised, locally advanced and metastatic CRC. Finally, we discuss how its widespread could transform CRC patients' management, dissecting its limitations while suggesting improvement strategies.
| S-EPMC9346106 | biostudies-literature
Project description:Precision medicine refers to the choosing of targeted therapies based on genetic data. Due to the increasing availability of data from large-scale tumor genome sequencing projects, genome-driven oncology may have enormous potential to change the clinical management of patients with cancer. To this end, components of tumors, which are shed into the circulation, i.e., circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or extracellular vesicles, are increasingly being used for monitoring tumor genomes. A growing number of publications have documented that these "liquid biopsies" are informative regarding response to given therapies, are capable of detecting relapse with lead time compared to standard measures, and reveal mechanisms of resistance. However, the majority of published studies relate to advanced tumor stages and the use of liquid biopsies for detection of very early malignant disease stages is less well documented. In early disease stages, strategies for analysis are in principle relatively similar to advanced stages. However, at these early stages, several factors pose particular difficulties and challenges, including the lower frequency and volume of aberrations, potentially confounding phenomena such as clonal expansions of non-tumorous tissues or the accumulation of cancer-associated mutations with age, and the incomplete insight into driver alterations. Here we discuss biology, technical complexities and clinical significance for early cancer detection and their impact on precision oncology.
| S-EPMC5871864 | biostudies-other
Project description:As lung cancer has the highest cancer-specific mortality rates worldwide, there is an urgent need for new therapeutic and diagnostic approaches to detect early-stage tumors and to monitor their response to the therapy. In addition to the well-established tissue biopsy analysis, liquid-biopsy-based assays may evolve as an important diagnostic tool. The analysis of circulating tumor DNA (ctDNA) is the most established method, followed by other methods such as the analysis of circulating tumor cells (CTCs), microRNAs (miRNAs), and extracellular vesicles (EVs). Both PCR- and NGS-based assays are used for the mutational assessment of lung cancer, including the most frequent driver mutations. However, ctDNA analysis might also play a role in monitoring the efficacy of immunotherapy and its recent accomplishments in the landscape of state-of-the-art lung cancer therapy. Despite the promising aspects of liquid-biopsy-based assays, there are some limitations regarding their sensitivity (risk of false-negative results) and specificity (interpretation of false-positive results). Hence, further studies are needed to evaluate the usefulness of liquid biopsies for lung cancer. Liquid-biopsy-based assays might be integrated into the diagnostic guidelines for lung cancer as a tool to complement conventional tissue sampling.
| S-EPMC10000706 | biostudies-literature
Project description:Recent omics analyses of human biofluids provide opportunities to probe selected species of biomolecules for disease diagnostics. Fourier-transform infrared (FTIR) spectroscopy investigates the full repertoire of molecular species within a sample at once. Here, we present a multi-institutional study in which we analysed infrared fingerprints of plasma and serum samples from 1639 individuals with different solid tumours and carefully matched symptomatic and non-symptomatic reference individuals. Focusing on breast, bladder, prostate, and lung cancer, we find that infrared molecular fingerprinting is capable of detecting cancer: training a support vector machine algorithm allowed us to obtain binary classification performance in the range of 0.78-0.89 (area under the receiver operating characteristic curve [AUC]), with a clear correlation between AUC and tumour load. Intriguingly, we find that the spectral signatures differ between different cancer types. This study lays the foundation for high-throughput onco-IR-phenotyping of four common cancers, providing a cost-effective, complementary analytical tool for disease recognition.
| S-EPMC8547961 | biostudies-literature
Project description:Molecular profiling of liquid biopsies is now emerging as pivotal for cancer biomarker discovery. The low-invasive nature of the approach used for collecting biospecimens (i.e. blood, urine, saliva, etc.) may allow a widespread application of novel molecular diagnostics based on liquid biopsies. This is relevant, for example, in cancer screening programmes where it is essential to reduce costs and the complexity of screening tests in order to increase study compliance and effectiveness. Here, I discuss recent advances in biomarkers for the early cancer detection and prediction of chemotherapy response based on the molecular profiling of liquid biopsies.
| S-EPMC4664509 | biostudies-literature
Project description:Currently the clinical management of breast cancer relies on relatively few prognostic/predictive clinical markers (estrogen receptor, progesterone receptor, HER2), based on primary tumor biology. Circulating biomarkers, such as circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) may enhance our treatment options by focusing on the very cells that are the direct precursors of distant metastatic disease, and probably inherently different than the primary tumor's biology. To shift the current clinical paradigm, assessing tumor biology in real time by molecularly profiling CTCs or ctDNA may serve to discover therapeutic targets, detect minimal residual disease and predict response to treatment. This review serves to elucidate the detection, characterization, and clinical application of CTCs and ctDNA with the goal of precision treatment of breast cancer.
| S-EPMC4850125 | biostudies-literature
Project description:In contrast to normal cells, tumor cells of multiple entities overexpress the Heat shock protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane Hsp70-positive tumor cells actively release Hsp70 in small extracellular vesicles with biophysical characteristics of exosomes. Due to conformational changes of Hsp70 in a lipid environment, most commercially available antibodies fail to detect membrane-bound and vesicular Hsp70. To fill this gap and to assess the role of vesicular Hsp70 in circulation as a potential tumor biomarker, we established the novel complete (comp)Hsp70 sandwich ELISA, using two monoclonal antibodies (mAbs), that is able to recognize both free and lipid-associated Hsp70 on the cell surface of viable tumor cells and on small extracellular vesicles. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70 with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/mL, high recovery rates of spiked liposomal Hsp70 (>84%), comparable values between human serum and plasma samples and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy donors. Hsp70 concentrations dropped concomitantly with a decrease in viable tumor mass upon irradiation of patients with approximately 20 Gy (range 18-22.5 Gy) and after completion of radiotherapy (60-70 Gy). In summary, the compHsp70 ELISA presented herein provides a sensitive and reliable tool for measuring free and vesicular Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a tumor-specific biomarker, for risk assessment (i.e., differentiation of grade III vs. IV adeno NSCLC) and monitoring of therapeutic outcomes.
| S-EPMC8345117 | biostudies-literature
Project description:Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872-0.931, p = 3.4 × 10-9) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies.
| S-EPMC10487078 | biostudies-literature
Project description:Colorectal cancer (CRC) is one of the top five cancers in incidence and mortality worldwide. The early detection of this neoplasm through analysis of circulating free DNA (cfDNA), which carries tumor genetic alterations, as a liquid biopsy, could have a major impact in enhancing early detection and reducing the mortality rate. The aim of this work was to demonstrate the feasibility of using cfDNA as a liquid biopsy for the early detection of CRC. For this purpose, we implemented an azoxymethane and dextran sodium sulfate-induced murine carcinogenesis model to detect oncogenic somatic mutations in Ctnnb1 and Kras during CRC development. To enhance the sensitivity in the detection, E-ice-COLD-PCR was utilized to selectively enrich for mutant alleles, followed by massively parallel sequencing. Driving somatic mutations were detected in Ctnnb1 and Kras in the liquid biopsies of early stages of tumor development, corresponding to the formation of aberrant crypt foci, the first histological alterations that can be identified throughout the formation of CRC. The concentration of cfDNA was increased along the carcinogenic process. Polyclonality in Ctnnb1 was found in tumor samples and cfDNA in this model. On the other hand, the use of cfDNA as a non-invasive test resulted in superior early detection compared to microPET/CT imaging. As a proof-of-principle, this study shows the great potential use of allelic-specific PCR for the detection and enrichment of pathogenic alleles present in cfDNA samples, as a test for early non-invasive detection of CRC. This work provides scientific evidence to set methodological bases that allow early detection of mutations in cfDNA obtained from plasma of CRC in humans.
| S-EPMC9608204 | biostudies-literature
Project description:Over the past two decades, liquid biopsy has been increasingly used as a supplement, or even, a replacement to the traditional biopsy in clinical oncological practice, due to its noninvasive and early detectable properties. The detections can be based on a variety of features extracted from tumor‑derived entities, such as quantitative alterations, genetic changes, and epigenetic aberrations, and so on. So far, the clinical applications of cancer liquid biopsy mainly aimed at two aspects, prediction (early diagnosis, prognosis and recurrent evaluation, therapeutic response monitoring, etc.) and intervention. In spite of the rapid development and great contributions achieved, cancer liquid biopsy is still a field under investigation and deserves more clinical practice. To better open up future work, here we systematically reviewed and compared the latest progress of the most widely recognized circulating components, including circulating tumor cells, cell-free circulating DNA, noncoding RNA, and nucleosomes, from their discovery histories to clinical values. According to the features applied, we particularly divided the contents into two parts, beyond epigenetics and epigenetic-based. The latter was considered as the highlight along with a brief overview of the advances in both experimental and bioinformatic approaches, due to its unique advantages and relatively lack of documentation.
| S-EPMC10363811 | biostudies-literature