bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B51: Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles
Authors: Everaert Celine , Helsmoortel Hetty , Decock Anneleen , Hulstaert Eva , Van Paemel Ruben , Verniers Kimberly , Nuytens Justine , Anckaert Jasper , Nijs Nele , Tulkens Joeri , Dhondt Bert , Hendrix An , Mestdagh Pieter , Vandesompele Jo 
Published: June 2020

Abstract
RNA profiling has emerged as a powerful tool to investigate the biomarker potential of human biofluids. Despite the interest in extracellular nucleic acids, RNA sequencing methods to quantify the total RNA content outside cells are rare. Therefore, we evaluated the performance of the SMARTer Stranded Total RNA-Seq method in human platelet-rich plasma, platelet-free plasma, urine, conditioned medium, and extracellular vesicles (EVs) from these biofluids. We found the method to be accurate, precise, compatible with low-input volumes, and able to quantify a few thousand genes. We picked up distinct classes of RNA molecules, including mRNA, lncRNA, circRNA, miscRNA, and pseudogenes. Notably, the read distribution and gene content drastically differed among biofluids. We also observed differences between EDTA and citrate platelet-free plasma, which are identical biofluids collected in different blood tubes and prepared with a slightly different centrifugation protocol. In conclusion, we are the first to show that the SMARTer method can be used for unbiased charting of the complete transcriptome of a wide range of biofluids and their extracellular vesicles. The advantage of the SMARTer Stranded Total RNA-Seq method is its potential to process low amounts of input material. Indeed, collecting samples is often the bottleneck in fundamental, (pre)clinical, or translational research projects, and being able to disseminate large amounts of information from only 200 μL (or less) can substantially impact research progress.
Citation Format: Celine Everaert, Hetty Helsmoortel, Anneleen Decock, Eva Hulstaert, Ruben Van Paemel, Kimberly Verniers, Justine Nuytens, Jasper Anckaert, Nele Nijs, Joeri Tulkens, Bert Dhondt, An Hendrix, Pieter Mestdagh, Jo Vandesompele. Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B51.
Abstract B55: PIK3CA mutation enrichment and detection in clinical samples
Authors: Keraite Ieva , Alvarez-Garcia Virginia , Favero Jurgen Del , Kersaudy-Kerhoas Maiwenn , Leslie Nicholas 
Published: June 2020

Abstract
The PI3K/AKT/mTOR signaling pathway is one of the most frequently mutated pathways in human cancers, including breast cancer. Given the current urge for more personalized approaches, there is an increasing need for a rigorous list of biomarkers and detection methods with advanced, less-invasive, reliable, and low-cost technologies. Despite limited clinical results to date, the detection of PIK3CA mutations shows great potential to contribute in cancer patient management in the future at many different levels, including diagnosis, treatment choice and monitoring, and identification of drug resistance. However, current molecular methods still lack analytical sensitivity to detect mutations of low abundance in high wild-type DNA background. Makrigiorgos et al. recently developed a nuclease-assisted minor-allele enrichment assay with overlapping probes, which is practical and cost-effective and allows detection of very-low-abundance mutations that could have relevance in the clinic. Thus we aimed to develop PIK3CA mutation-specific nuclease-based enrichment assay and validate it with tissue biopsy and blood samples using crystal dPCR as well as combine it with our developed Sybr Green real-time qPCR detection method (Alvarez-Garcia et al. 2018), which allows a quick detection of PIK3CA mutations in clinical samples at low cost.
Citation Format: Ieva Keraite, Virginia Alvarez-Garcia, Jurgen Del Favero, Maiwenn Kersaudy-Kerhoas, Nicholas Leslie. PIK3CA mutation enrichment and detection in clinical samples [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B55.
Abstract B65: Precompetitive collaboration on liquid biopsy for early cancer assessment
Authors: Sorbara Lynn , Wong David , Bob Carter , Cote Richard , Lee Hakho , Papadopoulos Nickolas , Patel Abhijit , Srivastava Sudhir 
Published: June 2020

Abstract
Precompetitive collaboration is a term used when competitors share early stages of research and development that are beneficial to all stakeholders. This Public-Private Partnership Consortium supports research to advance technologies and use these technologies for early cancer detection, to distinguish benign disease from cancer, and to distinguish aggressive from nonaggressive cancer. Combining the complementary expertise of both academics and industry may increase the likelihood of developing a viable diagnostic assay. In the era of personalized medicine, it is desirable to have noninvasive or minimally invasive methods to determine and follow longitudinally the molecular composition and characterization of a patient’s tumor, which will help gain a broader understanding of the disease. Liquid biopsy (CTC, ctDNA, extracellular vesicles, etc.) can be used to molecularly characterize the tumor and monitor genetic changes over time using repeat sampling of biofluids. The current technologies have shown great potential in diagnosis, predicting response to therapy, and monitoring relapse; however, the biologic and analytical challenges have rendered their usefulness for early detection/screening more difficult to establish. To address these challenges, the NCI developed this cooperative agreement program to support the work of six teams. Each team consists of a group of experts that include oncologists, bioinformaticians, researchers, and at least one industry partner. The current teams are developing a variety of unique assays/technologies that range from capture enhancements, microscope integration, nanoplasmonics, to specialized machine learning algorithms and bioinformatic analyses. Ovarian, breast, lung, and brain cancers are the model systems being studied, and there are at least two teams focused on each cancer type. The Consortium conducts work with the assistance of two working subgroups, Study Design and Biorepository, in conjunction with NCI staff. To monitor progress, there are yearly face-to-face Steering Committee meetings and monthly conference calls/Webex meetings. Progress in the first year of funding has been noteworthy. One of the teams has already achieved Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologists Certification, while another team has an insurance reimbursable extracellular vesicles test for risk assessment for prostate cancer.
Citation Format: Lynn Sorbara, David Wong, Carter Bob, Richard Cote, Hakho Lee, Nickolas Papadopoulos, Abhijit Patel, Sudhir Srivastava. Precompetitive collaboration on liquid biopsy for early cancer assessment [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B65.
Abstract IA01: Plasma DNA-based molecular diagnostics: Fragments, circles and beyond
Authors: Lo Yuk Ming Dennis 
Published: June 2020

Abstract
My group has a longstanding interest in the diagnostic applications of cell-free DNA in plasma. For example, we have pioneered noninvasive prenatal testing (NIPT) and the use of plasma DNA for cancer screening. We believe that understanding the fundamental biology of circulating DNA is essential to further advance the field. In this regard, we have been particularly interested in the fragmentation patterns of cell-free DNA in plasma. We have shown that cell-free fetal DNA molecules in the plasma of pregnant women are shorter than those of maternal origin. The differential size profiles between circulating fetal and maternal DNA have enabled the use of plasma DNA size as an independent metric for NIPT. In the area of cancer liquid biopsy, we have used circulating Epstein-Barr virus (EBV) DNA as an example of tumor-derived DNA in plasma. Hence, circulating EBV DNA molecules are also short fragments of DNA. In another example, we have used hepatocellular carcinoma as a model system and have found that circulating tumor-derived DNA molecules have a shorter size profile than those of nontumoral origin. We are exploring enzymes that might be involved in the fragmentation of plasma DNA. We have shown that mice in which both copies of the Dnase1l3 gene have been knocked out have a larger size profile of circulating DNA. We have also developed a plasma DNA end motif metric to measure the effect of disruption of this nuclease system. In addition to the fragmentation of linear DNA in plasma, my group is also interested in exploring the presence of nonlinear DNA in plasma. Hence, we have used mitochondrial DNA (mtDNA) as a model system as mtDNA exists as a circular molecule inside mitochondria. Interestingly, we have observed the existence of both linear and circular mtDNA in plasma. Using liver and bone marrow transplantation models, we have shown that the circular form is predominantly of hematopoietic origin while the linear form is predominantly from the liver. Plasma mtDNA topologics thus holds information on the origin of circulating DNA. These studies therefore demonstrate some of the exciting findings that can be revealed through the study of plasma DNA fragmentomics and topologics. We believe that such new biologic understandings will drive new diagnostic applications.
Citation Format: Yuk Ming Dennis Lo. Plasma DNA-based molecular diagnostics: Fragments, circles and beyond [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA01.
Abstract IA05: ctDNA and MRD in colorectal cancer: Time to reinvent adjuvant clinical trials
Authors: Tie Jeanne , Papadopoulos Nickolas , Kinzler Kenneth , Vogelstein Bert , Gibbs Peter 
Published: June 2020

Abstract
The most substantial opportunity for improving cancer survival outcomes is in the setting of early-stage disease, where evidence indicates that adjuvant chemotherapy can reduce recurrence and prevent cancer-related death through the eradication of minimal residual disease. However, the current stage-based treatment approach lacks precision and has quite a modest survival impact. A powerful prognostic marker could revolutionize adjuvant therapy by (i) better defining the recurrence risk of individual patients and allowing delivery of a more personalized treatment approach and (ii) enriching studies of new therapies with high-risk patients, substantially reducing the size and cost of adjuvant therapy trials. Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker, with the ability to detect minimal residual disease following curative intent treatment in early-stage colorectal cancer. I will discuss the potential clinical utilities of ctDNA in early-stage colorectal cancer, including ongoing biomarker-driven adjuvant randomized trials.
Citation Format: Jeanne Tie, Nickolas Papadopoulos, Kenneth Kinzler, Bert Vogelstein, Peter Gibbs. ctDNA and MRD in colorectal cancer: Time to reinvent adjuvant clinical trials [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA05.
Abstract IA13: Tracking and targeting colorectal cancer evolution
Authors: Bardelli Alberto 
Published: June 2020

Abstract
When metastatic cancers are challenged with targeted agents, almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances, targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near certainty of disease recurrence following treatment with targeted agents? Addressing this question means considering as a target not “only” individual oncogenes but also the evolving nature of human tumors. We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumors’ evolution, the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars. To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells, that is to say, therapies must adapt to tumor evolution. One possibility is to anticipate the changes the tumors will make. For example, by knowing in advance how CRC cells overcome resistance to EGFR blockade, we devised further rounds of therapy. These findings became the bases of clinical trials aimed at targeting cancer evolution and exploiting liquid biopsies to monitor the emergence of drug resistance and to design further lines of therapies.
Citation Format: Alberto Bardelli. Tracking and targeting colorectal cancer evolution [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA13.
Abstract IA16: Enhancing detection of ctDNA in patients with early-stage or residual disease
Authors: Rosenfeld Nitzan 
Published: June 2020

Abstract
Liquid biopsies have become a reality as part of the diagnostic toolbox for oncology. Assays based on targeted next-generation sequencing of circulating tumor DNA (ctDNA) are now reimbursed for genotyping of advanced disease and can be used to identify resistance mechanisms. I will describe some of our work in developing and validating such tests. I will also describe methods we have developed that leverage the characteristic fragment sizes of ctDNA to aid in detecting and monitoring cancer, using shallow whole-genome sequencing and by analysis of dried blood spots. Applications of ctDNA analysis as a diagnostic tool for earlier-stage disease are making exciting progress. Recent studies have shown potential for detection of minimal residual disease and monitoring for relapse in patients who have undergone treatment with curative intent. Current tests have shown excellent specificity and positive predictive value, and most patients relapse within 6-12 months after ctDNA is detected. These findings have supported the launching of clinical trials to test the utility of ctDNA-guided adjuvant treatment. Patients for whom ctDNA has not been detected with current methods still face an uncertain prognosis. I will describe our ongoing efforts to develop tests with enhanced sensitivity, which aim to identify a larger fraction of patients destined to recur, and to provide a longer lead time prior to clinically overt recurrence, when the residual disease has had less time to grow and evolve.
Citation Format: Nitzan Rosenfeld. Enhancing detection of ctDNA in patients with early-stage or residual disease [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA16.
Abstract IA18: Molecular signatures of circulating tumor cells
Authors: Haber Daniel , Hong Xin , Ebright Richard , Micalizi Doug , Bardia Aditya , Sullivan Ryan , Toner Mehmet , Maheswaran Shyamala 
Published: June 2020

Abstract
Circulating tumor cells (CTCs) are shed from primary cancers, as well as from metastatic deposits, into the blood circulation, where they may travel either as single cells or as CTC clusters, facing both mechanical and oxidative stress. Only a small subset of CTCs remain sufficiently viable to initiate metastatic growth upon dissemination to distant organs; their detection in patients with localized invasive cancer may present an opportunity for early detection, while their analysis in advanced cases provides a “whole cell biomarker,” enabling single-cell DNA, RNA, and protein studies, as well as functional drug-sensitivity testing using cultured CTCs. We have applied microfluidic technologies to deplete normal hematopoietic cells from blood specimens of patients with cancer, enhancing the ability of unmanipulated CTCs to proliferate ex vivo and recapitulating features of metastatic-competent cancer cells. Cultured CTCs from patients with either breast cancer or melanoma are highly tumorigenic when injected orthotopically at low inoculum into immunosuppressed mice. However, they display sensitivity to ROS and appear to upregulate compensatory mechanisms that are not commonly observed in primary tumors. In addition, they may undergo prolonged dormancy when lodged within distant organs. By combining single-cell RNA seq of patient-derived CTCs together with CRISPR and other genome-wide screens for modulators of metastasis phenotypes, we have sought to identify novel vulnerabilities in these cellular initiators of metastasis. While CTCs transit only very briefly through the blood circulation, these exceptional conditions may present new therapeutic opportunities to suppress the metastatic recurrence of cancer.
Citation Format: Daniel Haber, Xin Hong, Richard Ebright, Doug Micalizi, Aditya Bardia, Ryan Sullivan, Mehmet Toner, Shyamala Maheswaran. Molecular signatures of circulating tumor cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA18.
Abstract IA22: Tumor-educated platelets for the detection of cancer
Authors: Wurdinger Thomas 
Published: June 2020

Abstract
Blood-based “liquid biopsies” provide a means for minimally invasive molecular diagnostics, overcoming limitations of tissue acquisition. Early detection of cancer, clinical cancer diagnostics, and companion diagnostics are regarded as important applications of liquid biopsies. It has been reported that tumor-educated platelets (TEPs) may enable blood-based cancer diagnostics. Platelets have emerged as central players in the systemic and local responses to tumor growth. Confrontation of platelets with tumor cells via transfer of tumor-associated biomolecules (“education”) is an emerging concept and can result in the sequestration of biomolecules. Moreover, external stimuli induce specific splicing of pre-mRNAs in circulating platelets. Platelets are considered to undergo queue-specific splice events in response to signals released by cancer cells and the tumor microenvironment, such as stromal and immune cells. The combination of specific splice events in response to external signals and the capacity of platelets to directly ingest (spliced) circulating mRNA can provide TEPs with a highly dynamic mRNA repertoire, with potential applicability to cancer diagnostics. We determined the diagnostic potential of TEPs by mRNA sequencing of platelet samples. Blood platelet samples of &gt;1,000 patients with cancer covering multiple tumor types and healthy donors were analyzed. Healthy donors and early- and late-stage cancer patients were distinguished by a self-learning support vector machine (SVM) algorithm, using a set of spliced platelet transcripts with moderate to high expression. These results suggest that blood platelets may advance blood-based “liquid biopsies,” including for the detection of stage I-II tumors.
Citation Format: Thomas Wurdinger. Tumor-educated platelets for the detection of cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA22.
Abstract IA26: Liquid biopsy in precision pathology: Plasma and beyond!
Authors: Netto George J. 
Published: June 2020

Abstract
Launched in 2006, The Cancer Genome Atlas project (TCGA) aimed at systematically exploring the entire spectrum of genomic changes involved in human cancer. This year, the colossal effort culminated with the analysis of 11,000 cases across 33 tumor types. The comprehensive multiparametric (i.e., genomic, transcriptomic, epigenomic, and proteomic) analysis has yielded staggering datasets characterizing the molecular underpinning of human cancer types. This resulted in robust molecular classifications for common malignancies. A shared functional categorization of molecular alterations across tumor types has emerged, which offers a multitude of druggable targets.
As the list of actionable genetic alterations in solid and hematologic malignancies continue to grow, molecular diagnostic applications are rapidly penetrating the daily practice of the pathologist in an unparalleled pace. “Precision pathology” is now an integral part of the practice of “precision oncology.” Despite initial response, patients receiving targeted therapy will develop resistance due to clonal evolution and the acquired survival advantage of nonresponsive tumor clones. As a result, treated patients are increasingly subjected to longitudinal surveillance for clonal evolution in search of new targets.
The need for repeated tumor sampling for surveillance is driving the search for dynamic noninvasive tumor sampling methods. Non-tissue-based sampling methods (liquid biopsy) offer easy repeated access to tumor material in cancer patient body fluids for genomic analysis. Compared to traditional tissue biopsies, liquid biopsies also offer the advantage of “global” analysis of the often heterogeneous tumor genomic landscape both within primary and metastatic sites. The promise of liquid biopsy assays has fueled billions of dollars of investment from major biotechnology players.
The current seminar will discuss the principles of liquid biopsy technology. Challenges facing the applications of plasma and urine-based liquid biopsy techniques in precision pathology will be highlighted.
Citation Format: George J. Netto. Liquid biopsy in precision pathology: Plasma and beyond! [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA26.