Homogeneous Digital Biosensor for Circulating Tumor DNA by Enumerating Dual-color Quantum Dot Complex

The Analyst ◽  
2021 ◽  
Author(s):  
Xiaojun Liu ◽  
Zhangjian Wu ◽  
Xinyi Lin ◽  
Wei Bu ◽  
Lei Qin ◽  
...  

Monitoring ctDNA in blood is important to cancer management. Here, we develop a one-step single particle counting approach for directly quantifying ctDNA in plasma. Hairpin DNA containing a triple helix...

2019 ◽  
Vol 63 (6) ◽  
pp. 456-465 ◽  
Author(s):  
Joana Fernandes Marques ◽  
Joana Pereira Reis ◽  
Gabriela Fernandes ◽  
Venceslau Hespanhol ◽  
José Carlos Machado ◽  
...  

Liquid biopsy was introduced to the oncology field with the promise of revolutionizing the management of cancer patients, minimizing the exposure to invasive procedures such as tissue biopsy, and providing reliable information regarding therapy response and detection of disease relapse. Despite the significant increase in the number of published studies on circulating tumor DNA (ctDNA) in the past years, the emphasis of most studies is on the development of new technologies or on the clinical utility of ctDNA. This leaves a clear gap of knowledge concerning the biology of ctDNA, such as the fundamental mechanisms through which DNA from tumor cells is released into the circulation. Moreover, considering that ctDNA analysis is now currently being applied in clinical practice, the need for rigorous quality control is arising, and with it the necessity to standardize procedures, from sample collection to data analysis. This review focuses on the main aspects of ctDNA, including approaches currently available to evaluate tumor genetics, as well as the points that still require improvement in order to make liquid biopsy a key player in precision medicine.


Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 550
Author(s):  
Julius Wehrle ◽  
Ulrike Philipp ◽  
Martina Jolic ◽  
Marie Follo ◽  
Saskia Hussung ◽  
...  

Background: Circulating tumor DNA (ctDNA) in the blood plasma of cancer patients is an emerging biomarker used across oncology, facilitating noninvasive disease monitoring and genetic profiling at various disease milestones. Digital droplet PCR (ddPCR) technologies have demonstrated high sensitivity and specificity for robust ctDNA detection at relatively low costs. Yet, their value for ctDNA-based management of a broad population of cancer patients beyond clinical trials remains elusive. Methods: We developed mutation-specific ddPCR assays that were optimized for their use in real-world cancer management, covering 12 genetic aberrations in common cancer genes, such as EGFR, BRAF, KIT, KRAS, and NRAS. We assessed the limit of detection (LOD) and the limit of blank (LOB) for each assay and validated their performance for ctDNA detection using matched tumor sequencing. Results: We applied our custom ddPCR assays to 352 plasma samples from 96 patients with solid tumors. Mutation detection in plasma was highly concordant with tumor sequencing, demonstrating high sensitivity and specificity across all assays. In 20 cases, radiographic cancer progression was mirrored by an increase of ctDNA concentrations or the occurrence of novel mutations in plasma. Moreover, ctDNA profiling at diagnosis and during disease progression reflected personalized treatment selection through the identification of actionable gene targets in 20 cases. Conclusion: Collectively, our work highlights the potential of ctDNA assessment by sensitive ddPCR for accurate disease monitoring, robust identification of resistance mutations, and upfront treatment selection in patients with solid tumors. We envision an increasing future role for ctDNA profiling within personalized cancer management in daily clinical routine.


Blood ◽  
2019 ◽  
Vol 133 (22) ◽  
pp. 2359-2364 ◽  
Author(s):  
Sjors G. J. G. In ‘t Veld ◽  
Thomas Wurdinger

Abstract Liquid biopsies have been considered the holy grail in achieving effective cancer management, with blood tests offering a minimally invasive, safe, and sensitive alternative or complementary approach for tissue biopsies. Currently, blood-based liquid biopsy measurements focus on the evaluation of biomarker types, including circulating tumor DNA, circulating tumor cells, extracellular vesicles (exosomes and oncosomes), and tumor-educated platelets (TEPs). Despite the potential of individual techniques, each has its own advantages and disadvantages. Here, we provide further insight into TEPs.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4743
Author(s):  
Emilie Moati ◽  
Valerie Taly ◽  
Simon Garinet ◽  
Audrey Didelot ◽  
Julien Taieb ◽  
...  

Gastrointestinal (GI) cancers are major health burdens worldwide and biomarkers are needed to improve the management of these diseases along their evolution. Circulating tumor DNA (ctDNA) is a promising non-invasive blood and other bodily-fluid-based biomarker in cancer management that can help clinicians in various cases for the detection, diagnosis, prognosis, monitoring and personalization of treatment in digestive oncology. In addition to the well-studied prognostic role of ctDNA, the main real-world applications appear to be the assessment of minimal residual disease to further guide adjuvant therapy and predict relapse, but also the monitoring of clonal evolution to tailor treatments in metastatic setting. Other challenges such as predicting response to treatment including immune checkpoint inhibitors could also be among the potential applications of ctDNA. Although the level of advancement of ctDNA development in the different tumor localizations is still inhomogeneous, it might be now reliable enough to be soon used in clinical routine for colorectal cancers and shows promising results in other GI cancers.


2019 ◽  
Vol 1871 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Ziyang Li ◽  
Lang Yi ◽  
Peng Gao ◽  
Rui Zhang ◽  
Jinming Li

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3443
Author(s):  
Ayanthi A. Wijewardene ◽  
Marthe Chehade ◽  
Matti L. Gild ◽  
Roderick J. Clifton-Bligh ◽  
Martyn Bullock

Liquid biopsies are a novel technique to assess for either circulating tumor cells (CTC) or circulating tumor DNA (ctDNA and microRNA (miRNA)) in peripheral blood samples of cancer patients. The diagnostic role of liquid biopsy in oncology has expanded in recent years, particularly in lung, colorectal and breast cancer. In thyroid cancer, the role of liquid biopsy in either diagnosis or prognosis is beginning to translate from the lab to the clinic. In this review, we describe the evolution of liquid biopsies in detecting CTC, ctDNA and miRNA in thyroid cancer patients, together with its limitations and future directions in clinical practice.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770574 ◽  
Author(s):  
C Nadal ◽  
T Winder ◽  
A Gerger ◽  
David Tougeron

Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.


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