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Liquid Biopsies in Oncology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 58622

Special Issue Editors

Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Interests: breast cancer; circulating tumor cells (CTCs); cell-free DNA (cfDNA); cell-tumor DNA (ctDNA); liquid biopsies; genetic variants
Special Issues, Collections and Topics in MDPI journals
Department of Clinical and Experimental Medicine, University of Study of Foggia, 71122 Foggia, Italy
Interests: precision medicine; personalized medicine; cancer genomics; genomics; liquid biopsy; molecular diagnostic; laboratory medicine; clinical molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the era of precision oncology, tumor molecular characterization plays a key role in selecting the right treatment for each patient at the right time. Technological advances, particularly next-generation sequencing (NGS), have paved the way to personalized medicine, reducing the time and costs required to assess the tumor’s genetic profile. Unfortunately, in some cases, tumor biopsies are not feasible, due to insufficient or inaccessible material.  The use of liquid biopsies has revolutionized the standard clinical approach by allowing the detection of different circulating molecules in the bloodstream and other body fluids, which may have a key role in diagnosing and monitoring the evolution of the tumor, and evaluating the response or resistance to the treatment. Since their FDA approval in 2016, for a therapy-guiding blood-based test to detect EGFR mutations in lung cancer patients, liquid biopsies are emerging as the standard of care. Liquid biopsies have several advantages, including minimal invasiveness and repeatability, which could guarantee a dynamic picture of the tumor and the chance to monitor pharmacological responses to the biopsy.

We invite scientists to submit original research focused on the application of liquid biopsies as an innovative tool in cancer diagnosis and monitoring, as well as its possible application in clinical practice. Articles may also be focused on understanding how circulating molecules offer new therapeutic strategies in cancer treatment. Review articles that describe the state of the art on this topic are also encouraged. This Special Issue, focusing on liquid biopsies in oncology, includes the use of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), circulating tumor RNAs (ctRNAs) as well as miRNAs, and extracellular vesicles (EVs). The topics of interest for this Special Issue include, but are not limited to, the following:

  • Liquid biopsy for cancer screening, diagnosis, prognosis, follow-up and therapeutic management of tumors;
  • Liquid biopsy for stratification and monitoring of cancer patients;
  • Liquid biopsy for the detection of actionable oncogenic mutations in cancers;
  • Liquid biopsy targeting ctDNA for molecular diagnosis of cancer;
  • Clinical validity and utility of ctDNA and ctRNA for tumor analysis;
  • Extracellular vesicle biomarkers;
  • New techniques to evaluate cell-free molecules;
  • Liquid biopsy on exosome for cancer diagnosis;
  • Liquid biopsies and epigenetics.

Dr. Sandra V. Fernandez
Dr. Carmela Paolillo
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • precision oncology
  • personalized therapy
  • cancer biomarkers
  • liquid biopsy
  • biological fluids
  • circulating molecules
  • circulating tumor cells
  • CTCs
  • ctDNA
  • ctRNA
  • cell-free DNA
  • cfDNA
  • NGS
  • circulating miRNAs
  • exosomes
  • extracellular vesicles

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Published Papers (18 papers)

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Research

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19 pages, 2989 KiB  
Article
Enumeration and Characterization of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization
by María L. Espejo-Cruz, Sandra González-Rubio, Juan J. Espejo, Javier M. Zamora-Olaya, Rafael M. Alejandre-Altamirano, María Prieto-Torre, Clara I. Linares, Marta Guerrero-Misas, Pilar Barrera-Baena, Antonio Poyato-González, Marina Sánchez-Frías, María D. Ayllón, Manuel L. Rodríguez-Perálvarez, Manuel de la Mata and Gustavo Ferrín
Int. J. Mol. Sci. 2023, 24(3), 2558; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032558 - 29 Jan 2023
Viewed by 2196
Abstract
Circulating tumor cells (CTCs), and particularly circulating cancer stem cells (cCSC), are prognostic biomarkers for different malignancies and may be detected using liquid biopsies. The ex vivo culture of cCSCs would provide valuable information regarding biological aggressiveness and would allow monitoring the adaptive [...] Read more.
Circulating tumor cells (CTCs), and particularly circulating cancer stem cells (cCSC), are prognostic biomarkers for different malignancies and may be detected using liquid biopsies. The ex vivo culture of cCSCs would provide valuable information regarding biological aggressiveness and would allow monitoring the adaptive changes acquired by the tumor in real time. In this prospective pilot study, we analyzed the presence of EpCAM+ CTCs using the IsoFlux system in the peripheral blood of 37 patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE). The average patient age was 63.5 ± 7.9 years and 91.9% of the patients were men. All patients had detectable CTCs at baseline and 20 patients (54.1%) showed CTC aggregates or clusters in their peripheral blood. The increased total tumor diameter (OR: 2.5 (95% CI: 1.3–4.8), p = 0.006) and the absence of clusters of CTCs at baseline (OR: 0.2 (95% CI: 0.0–1.0), p = 0.049) were independent predictors of a diminished response to TACE. Culture of cCSC was successful in five out of thirty-three patients, mostly using negative enrichment of CD45 cells, ultra-low adherence, high glucose, and a short period of hypoxia followed by normoxia. In conclusion, the identification of clusters of CTCs before TACE and the implementation of standardized approaches for cCSC culture could aid to predict outcomes and to define the optimal adjuvant therapeutic strategy for a true personalized medicine in hepatocellular carcinoma. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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16 pages, 985 KiB  
Article
A Novel Detection Method of Breast Cancer through a Simple Panel of Biomarkers
by Alinne T. F. Silva, Cláudia M. Rodrigues, Izabella C. C. Ferreira, Letícia L. D. Santos, Donizeti W. Santos, Thaise G. Araújo, Paula P. L. Canto, Carlos E. Paiva, Luiz R. Goulart and Yara C. P. Maia
Int. J. Mol. Sci. 2022, 23(19), 11983; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911983 - 09 Oct 2022
Viewed by 2343
Abstract
Circulating tumor cells (CTCs) have been identified as responsible for the spread of tumors to other organs of the body. In this sense, the development of sensitive and specific assays for their detection is important to reduce the number of deaths due to [...] Read more.
Circulating tumor cells (CTCs) have been identified as responsible for the spread of tumors to other organs of the body. In this sense, the development of sensitive and specific assays for their detection is important to reduce the number of deaths due to metastases. Here, we assessed whether the detection of CTCs in peripheral blood can serve in the construction of a panel of diagnosis and monitoring treatments of breast cancer (BC), focusing on the expression of markers of epithelial–mesenchymal transition. Through analyzing the blood from women without breast alterations (control), women with benign alterations, women with breast cancer without chemotherapy, and women with breast cancer with chemotherapy, we identified the best markers by transcriptional levels and determined three profiles of CTCs (mesenchymal, intermediate, and epithelial) by flow cytometry which, combined, can be used for diagnosis and therapy monitoring with sensitivity and specificity between 80% and 100%. Therefore, we have developed a method for detecting breast cancer based on the analysis of CTC profiles by epithelial–mesenchymal transition markers which, combined, can be used for the diagnosis and monitoring of therapy. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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12 pages, 1740 KiB  
Article
Cell-Free DNA as a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer
by Raquel Carrasco, Mercedes Ingelmo-Torres, Ascensión Gómez, Ramón Trullas, Fiorella L. Roldán, Tarek Ajami, Davinia Moreno, Leonardo Rodríguez-Carunchio, Antonio Alcaraz, Laura Izquierdo and Lourdes Mengual
Int. J. Mol. Sci. 2022, 23(19), 11732; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911732 - 03 Oct 2022
Cited by 6 | Viewed by 1588
Abstract
Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples [...] Read more.
Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients’ clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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13 pages, 2695 KiB  
Article
Comprehensive Genomic Profiling (CGP)-Informed Personalized Molecular Residual Disease (MRD) Detection: An Exploratory Analysis from the PREDATOR Study of Metastatic Colorectal Cancer (mCRC) Patients Undergoing Surgical Resection
by Sara Lonardi, Halla Nimeiri, Chang Xu, Daniel R. Zollinger, Russell W. Madison, Alexander D. Fine, Ole Gjoerup, Cosimo Rasola, Valentina Angerilli, Shruti Sharma, Hsin-Ta Wu, Charuta C. Palsuledesai, Meenakshi Malhotra, Alexey Aleshin, Fotios Loupakis, Elise Renkonen, Priti Hegde and Matteo Fassan
Int. J. Mol. Sci. 2022, 23(19), 11529; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911529 - 29 Sep 2022
Cited by 11 | Viewed by 4157
Abstract
A majority of patients with metastatic colorectal cancer (mCRC) experience recurrence post curative-intent surgery. The addition of adjuvant chemotherapy has shown to provide limited survival benefits when applied to all patients. Therefore, a biomarker to assess molecular residual disease (MRD) accurately and guide [...] Read more.
A majority of patients with metastatic colorectal cancer (mCRC) experience recurrence post curative-intent surgery. The addition of adjuvant chemotherapy has shown to provide limited survival benefits when applied to all patients. Therefore, a biomarker to assess molecular residual disease (MRD) accurately and guide treatment selection is highly desirable for high-risk patients. This feasibility study evaluated the prognostic value of a tissue comprehensive genomic profiling (CGP)-informed, personalized circulating tumor DNA (ctDNA) assay (FoundationOne®Tracker) (Foundation Medicine, Inc., Cambridge, MA, USA) by correlating MRD status with clinical outcomes. ctDNA analysis was performed retrospectively on plasma samples from 69 patients with resected mCRC obtained at the MRD and the follow-up time point. Tissue CGP identified potentially actionable alterations in 54% (37/69) of patients. MRD-positivity was significantly associated with lower disease-free survival (DFS) (HR: 4.97, 95% CI: 2.67–9.24, p < 0.0001) and overall survival (OS) (HR: 27.05, 95% CI: 3.60–203.46, p < 0.0001). Similarly, ctDNA positive status at the follow-up time point correlated with a marked reduction in DFS (HR: 8.78, 95% CI: 3.59–21.49, p < 0.0001) and OS (HR: 20.06, 95% CI: 2.51–160.25, p < 0.0001). The overall sensitivity and specificity at the follow-up time point were 69% and 100%, respectively. Our results indicate that MRD detection using the tissue CGP-informed ctDNA assay is prognostic of survival outcomes in patients with resected mCRC. The concurrent MRD detection and identification of actionable alterations has the potential to guide perioperative clinical decision-making. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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13 pages, 2212 KiB  
Article
Tumor-Informed Approach Improved ctDNA Detection Rate in Resected Pancreatic Cancer
by Kazunori Watanabe, Toru Nakamura, Yasutoshi Kimura, Masayo Motoya, Shigeyuki Kojima, Tomotaka Kuraya, Takeshi Murakami, Tsukasa Kaneko, Yoshihito Shinohara, Yosuke Kitayama, Keito Fukuda, Kanako C. Hatanaka, Tomoko Mitsuhashi, Fabio Pittella-Silva, Toshikazu Yamaguchi, Satoshi Hirano, Yusuke Nakamura and Siew-Kee Low
Int. J. Mol. Sci. 2022, 23(19), 11521; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911521 - 29 Sep 2022
Cited by 3 | Viewed by 2081
Abstract
Pancreatic cancer is one of the cancers with very poor prognosis; there is an urgent need to identify novel biomarkers to improve its clinical outcomes. Circulating tumor DNA (ctDNA) from liquid biopsy has arisen as a promising biomarker for cancer detection and surveillance. [...] Read more.
Pancreatic cancer is one of the cancers with very poor prognosis; there is an urgent need to identify novel biomarkers to improve its clinical outcomes. Circulating tumor DNA (ctDNA) from liquid biopsy has arisen as a promising biomarker for cancer detection and surveillance. However, it is known that the ctDNA detection rate in resected pancreatic cancer is low compared with other types of cancer. In this study, we collected paired tumor and plasma samples from 145 pancreatic cancer patients. Plasma samples were collected from 71 patients of treatment-naïve status and from 74 patients after neoadjuvant therapy (NAT). Genomic profiling of tumor DNA and plasma samples was conducted using targeted next-generation sequencing (NGS). Somatic mutations were detected in 85% (123/145) of tumors. ctDNA was detected in 39% (28/71) and 31% (23/74) of treatment-naïve and after-NAT groups, respectively, without referring to the information of tumor profiles. With a tumor-informed approach (TIA), ctDNA detection rate improved to 56% (40/71) and 36% (27/74) in treatment-naïve and after-NAT groups, respectively, with the detection rate significantly improved (p = 0.0165) among the treatment-naïve group compared to the after-NAT group. Cases who had detectable plasma ctDNA concordant to the corresponding tumor showed significantly shorter recurrence-free survival (RFS) (p = 0.0010). We demonstrated that TIA improves ctDNA detection rate in pancreatic cancer, and that ctDNA could be a potential prognostic biomarker for recurrence risk prediction Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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11 pages, 1605 KiB  
Article
Beta 2-Adrenergic Receptor in Circulating Cancer-Associated Cells Predicts for Increases in Stromal Macrophages in Circulation and Patient Survival in Metastatic Breast Cancer
by Kirby P. Gardner, Massimo Cristofanilli, Saranya Chumsri, Rena Lapidus, Cha-Mei Tang, Ashvathi Raghavakaimal and Daniel L. Adams
Int. J. Mol. Sci. 2022, 23(13), 7299; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137299 - 30 Jun 2022
Cited by 2 | Viewed by 1837
Abstract
The usage of beta blockers in breast cancer (BC) patients is implicated in the reduction in distant metastases, cancer recurrence, and cancer mortality. Studies suggest that the adrenergic pathway is directly involved in sympathetic-driven hematopoietic activation of pro-tumor microenvironmental proliferation and tumor cell [...] Read more.
The usage of beta blockers in breast cancer (BC) patients is implicated in the reduction in distant metastases, cancer recurrence, and cancer mortality. Studies suggest that the adrenergic pathway is directly involved in sympathetic-driven hematopoietic activation of pro-tumor microenvironmental proliferation and tumor cell trafficking into the circulation. Cancer-associated macrophage-like cells (CAMLs) are pro-tumor polynucleated monocytic cells of hematopoietic origin emanating from tumors which may aid in circulating tumor cell (CTC) dissemination into the circulation. We examined the linkage between Beta-2 adrenergic receptor (B2AR) signaling in CAMLs and CTCs by establishing expression profiles in a model BC cell line (MDA-MB-231). We compared the model to CAMLs and CTCs found in patents. Although internalization events were observed in patients, differences were found in the expression of B2AR between the tumor cell lines and the CAMLs found in patients. High B2AR expression on patients’ CAMLs was correlated with significantly more CAMLs in the circulation (p = 0.0093), but CTCs had no numerical relationship (p = 0.1565). High B2AR CAML expression was also significantly associated with a larger size of CAMLs (p = 0.0073), as well as being significantly associated with shorter progression-free survival (p = 0.0097) and overall survival (p = 0.0265). These data suggest that B2AR expression on CAMLs is closely related to the activation, intravasation, and growth of CAMLs in the circulation. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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17 pages, 1989 KiB  
Article
A Liquid Biopsy-Based Approach for Monitoring Treatment Response in Post-Operative Colorectal Cancer Patients
by Barbara Kinga Barták, Tamás Fodor, Alexandra Kalmár, Zsófia Brigitta Nagy, Sára Zsigrai, Krisztina Andrea Szigeti, Gábor Valcz, Péter Igaz, Magdolna Dank, István Takács and Béla Molnár
Int. J. Mol. Sci. 2022, 23(7), 3774; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073774 - 29 Mar 2022
Cited by 6 | Viewed by 2126
Abstract
Monitoring the therapeutic response of colorectal cancer (CRC) patients is crucial to determine treatment strategies; therefore, we constructed a liquid biopsy-based approach for tracking tumor dynamics in non-metastatic (nmCRC) and metastatic (mCRC) patients (n = 55). Serial blood collections were performed during [...] Read more.
Monitoring the therapeutic response of colorectal cancer (CRC) patients is crucial to determine treatment strategies; therefore, we constructed a liquid biopsy-based approach for tracking tumor dynamics in non-metastatic (nmCRC) and metastatic (mCRC) patients (n = 55). Serial blood collections were performed during chemotherapy for measuring the amount and the global methylation pattern of cell-free DNA (cfDNA), the promoter methylation of SFRP2 and SDC2 genes, and the plasma homocysteine level. The average cfDNA amount was higher (p < 0.05) in nmCRC patients with recurrent cancer (30.4 ± 17.6 ng) and mCRC patients with progressive disease (PD) (44.3 ± 34.5 ng) compared to individuals with remission (13.2 ± 10.0 ng) or stable disease (12.5 ± 3.4 ng). More than 10% elevation of cfDNA from first to last sample collection was detected in all recurrent cases and 92% of PD patients, while a decrease was observed in most patients with remission. Global methylation level changes indicated a decline (75.5 ± 3.4% vs. 68.2 ± 8.4%), while the promoter methylation of SFRP2 and SDC2 and homocysteine level (10.9 ± 3.4 µmol/L vs. 13.7 ± 4.3 µmol/L) presented an increase in PD patients. In contrast, we found exact opposite changes in remission cases. Our study offers a more precise blood-based approach to monitor the treatment response to different chemotherapies than the currently used markers. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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Review

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25 pages, 2137 KiB  
Review
Advances in Liquid Biopsy Technology and Implications for Pancreatic Cancer
by Alexander G. Raufi, Michael S. May, Matthew J. Hadfield, Attila A. Seyhan and Wafik S. El-Deiry
Int. J. Mol. Sci. 2023, 24(4), 4238; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24044238 - 20 Feb 2023
Cited by 15 | Viewed by 3258
Abstract
Pancreatic cancer is a highly aggressive malignancy with a climbing incidence. The majority of cases are detected late, with incurable locally advanced or metastatic disease. Even in individuals who undergo resection, recurrence is unfortunately very common. There is no universally accepted screening modality [...] Read more.
Pancreatic cancer is a highly aggressive malignancy with a climbing incidence. The majority of cases are detected late, with incurable locally advanced or metastatic disease. Even in individuals who undergo resection, recurrence is unfortunately very common. There is no universally accepted screening modality for the general population and diagnosis, evaluation of treatment response, and detection of recurrence relies primarily on the use of imaging. Identification of minimally invasive techniques to help diagnose, prognosticate, predict response or resistance to therapy, and detect recurrence are desperately needed. Liquid biopsies represent an emerging group of technologies which allow for non-invasive serial sampling of tumor material. Although not yet approved for routine use in pancreatic cancer, the increasing sensitivity and specificity of contemporary liquid biopsy platforms will likely change clinical practice in the near future. In this review, we discuss the recent technological advances in liquid biopsy, focusing on circulating tumor DNA, exosomes, microRNAs, and circulating tumor cells. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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16 pages, 1009 KiB  
Review
Copy Number Variations as Determinants of Colorectal Tumor Progression in Liquid Biopsies
by Jessica Debattista, Laura Grech, Christian Scerri and Godfrey Grech
Int. J. Mol. Sci. 2023, 24(2), 1738; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021738 - 16 Jan 2023
Cited by 2 | Viewed by 2403
Abstract
Over the years, increasing evidence has shown that copy number variations (CNVs) play an important role in the pathogenesis and prognosis of Colorectal Cancer (CRC). Colorectal adenomas are highly prevalent lesions, but only 5% of these adenomas ever progress to carcinoma. This review [...] Read more.
Over the years, increasing evidence has shown that copy number variations (CNVs) play an important role in the pathogenesis and prognosis of Colorectal Cancer (CRC). Colorectal adenomas are highly prevalent lesions, but only 5% of these adenomas ever progress to carcinoma. This review summarizes the different CNVs associated with adenoma-carcinoma CRC progression and with CRC staging. Characterization of CNVs in circulating free-RNA and in blood-derived exosomes augers well with the potential of using such assays for patient management and early detection of metastasis. To overcome the limitations related to tissue biopsies and tumor heterogeneity, using CNVs to characterize tumor-derived materials in biofluids provides less invasive sampling methods and a sample that collectively represents multiple tumor sites in heterogeneous samples. Liquid biopsies provide a source of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), tumor-derived exosomes (TDE), circulating free RNA, and non-coding RNA. This review provides an overview of the current diagnostic and predictive models from liquid biopsies. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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22 pages, 861 KiB  
Review
Circulating Histones to Detect and Monitor the Progression of Cancer
by Desislava K. Tsoneva, Martin N. Ivanov, Nikolay Vladimirov Conev, Rostislav Manev, Dragomir Svetozarov Stoyanov and Manlio Vinciguerra
Int. J. Mol. Sci. 2023, 24(2), 942; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24020942 - 04 Jan 2023
Cited by 9 | Viewed by 2296
Abstract
Liquid biopsies have emerged as a minimally invasive cancer detection and monitoring method, which could identify cancer-related alterations in nucleosome or histone levels and modifications in blood, saliva, and urine. Histones, the core component of the nucleosome, are essential for chromatin compaction and [...] Read more.
Liquid biopsies have emerged as a minimally invasive cancer detection and monitoring method, which could identify cancer-related alterations in nucleosome or histone levels and modifications in blood, saliva, and urine. Histones, the core component of the nucleosome, are essential for chromatin compaction and gene expression modulation. Increasing evidence suggests that circulating histones and histone complexes, originating from cell death or immune cell activation, could act as promising biomarkers for cancer detection and management. In this review, we provide an overview of circulating histones as a powerful liquid biopsy approach and methods for their detection. We highlight current knowledge on circulating histones in hematologic malignancies and solid cancer, with a focus on their role in cancer dissemination, monitoring, and tumorigenesis. Last, we describe recently developed strategies to identify cancer tissue-of-origin in blood plasma based on nucleosome positioning, inferred from nucleosomal DNA fragmentation footprint, which is independent of the genetic landscape. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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16 pages, 1695 KiB  
Review
Enzymatic Methods for Mutation Detection in Cancer Samples and Liquid Biopsies
by Farzaneh Darbeheshti and G. Mike Makrigiorgos
Int. J. Mol. Sci. 2023, 24(2), 923; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24020923 - 04 Jan 2023
Viewed by 2815
Abstract
Low-level tumor somatic DNA mutations in tissue and liquid biopsies obtained from cancer patients can have profound implications for development of metastasis, prognosis, choice of treatment, follow-up, or early cancer detection. Unless detected, such low-frequency DNA alterations can misinform patient management decisions or [...] Read more.
Low-level tumor somatic DNA mutations in tissue and liquid biopsies obtained from cancer patients can have profound implications for development of metastasis, prognosis, choice of treatment, follow-up, or early cancer detection. Unless detected, such low-frequency DNA alterations can misinform patient management decisions or become missed opportunities for personalized medicine. Next-generation sequencing technologies and digital-PCR can resolve low-level mutations but require access to specialized instrumentation, time, and resources. Enzymatic-based approaches to detection of low-level mutations provide a simple, straightforward, and affordable alternative to enrich and detect such alterations and is broadly available to low-resource laboratory settings. This review summarizes the traditional uses of enzymatic mutation detection and describes the latest exciting developments, potential, and applications with specific reference to the field of liquid biopsy in cancer. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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22 pages, 1323 KiB  
Review
Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer
by Ana Julia Aguiar de Freitas, Rhafaela Lima Causin, Muriele Bertagna Varuzza, Stéphanie Calfa, Cassio Murilo Trovo Hidalgo Filho, Tatiana Takahasi Komoto, Cristiano de Pádua Souza and Márcia Maria Chiquitelli Marques
Int. J. Mol. Sci. 2022, 23(17), 9952; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179952 - 01 Sep 2022
Cited by 26 | Viewed by 4644
Abstract
Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized [...] Read more.
Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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24 pages, 1293 KiB  
Review
Making the Rounds: Exploring the Role of Circulating Tumor DNA (ctDNA) in Non-Small Cell Lung Cancer
by Misty Dawn Shields, Kevin Chen, Giselle Dutcher, Ishika Patel and Bruna Pellini
Int. J. Mol. Sci. 2022, 23(16), 9006; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169006 - 12 Aug 2022
Cited by 11 | Viewed by 5186
Abstract
Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the [...] Read more.
Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for advanced NSCLC. ctDNA technologies have also shown the ability to detect the emerging mechanisms of acquired resistance that evolve after targeted therapy. Furthermore, the detection of minimal residual disease (MRD) by ctDNA for patients with NSCLC after curative-intent treatment may serve as a prognostic and potentially predictive biomarker for recurrence and response to therapy, respectively. Finally, ctDNA analysis via mutational, methylation, and/or fragmentation multi-omic profiling offers the potential for improving early lung cancer detection. In this review, we discuss the role of ctDNA in each of these capacities, namely, for molecular profiling, treatment response monitoring, MRD detection, and early cancer detection of NSCLC. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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42 pages, 820 KiB  
Review
A Liquid Biopsy in Bladder Cancer—The Current Landscape in Urinary Biomarkers
by Milena Matuszczak, Adam Kiljańczyk and Maciej Salagierski
Int. J. Mol. Sci. 2022, 23(15), 8597; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158597 - 02 Aug 2022
Cited by 16 | Viewed by 3829
Abstract
The non-muscle invasive bladder cancer tends to recur and progress. Therefore, it requires frequent follow-ups, generating costs and making it one of the most expensive neoplasms. Considering the expensive and invasive character of the current gold-standard diagnostic procedure, white-light cystoscopy, efforts to find [...] Read more.
The non-muscle invasive bladder cancer tends to recur and progress. Therefore, it requires frequent follow-ups, generating costs and making it one of the most expensive neoplasms. Considering the expensive and invasive character of the current gold-standard diagnostic procedure, white-light cystoscopy, efforts to find an alternative method are ongoing. Although the last decade has seen significant advancements in urinary biomarker tests (UBTs) for bladder cancer, international guidelines have not recommended them. Currently, the paramount urgency is to find and validate the test with the best specificity and sensitivity, which would allow for the optimizing of diagnosis, prognosis, and a treatment plan. This review aims to summarise the up-to-date state of knowledge relating to UBTs and new developments in the detection, prognosis, and surveillance of bladder cancer and their potential applications in clinical practice. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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23 pages, 700 KiB  
Review
Applications of Circulating Tumor Cells and Circulating Tumor DNA in Precision Oncology for Breast Cancers
by Sridevi Addanki, Salyna Meas, Vanessa Nicole Sarli, Balraj Singh and Anthony Lucci
Int. J. Mol. Sci. 2022, 23(14), 7843; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147843 - 16 Jul 2022
Cited by 15 | Viewed by 3137
Abstract
Liquid biopsies allow for the detection of cancer biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Elevated levels of these biomarkers during cancer treatment could potentially serve as indicators of cancer progression and shed light on the mechanisms of [...] Read more.
Liquid biopsies allow for the detection of cancer biomarkers such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Elevated levels of these biomarkers during cancer treatment could potentially serve as indicators of cancer progression and shed light on the mechanisms of metastasis and therapy resistance. Thus, liquid biopsies serve as tools for cancer detection and monitoring through a simple, non-invasive blood draw, allowing multiple longitudinal sampling. These circulating markers have significant prospects for use in assessing patients’ prognosis, monitoring response to therapy, and developing precision medicine. In addition, single-cell omics of these liquid biopsy markers can be potential tools for identifying tumor heterogeneity and plasticity as well as novel therapeutic targets. In this review, we focus on our current understanding of circulating tumor biomarkers, especially in breast cancer, and the scope of novel sequencing technologies and diagnostic methods for better prognostication and patient stratification to improve patient outcomes. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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17 pages, 769 KiB  
Review
Basic Science with Preclinical Models to Investigate and Develop Liquid Biopsy: What Are the Available Data and Is It a Fruitful Approach?
by Benedetta Cena, Emmanuel Melloul, Nicolas Demartines, Olivier Dormond and Ismail Labgaa
Int. J. Mol. Sci. 2022, 23(10), 5343; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23105343 - 10 May 2022
Cited by 3 | Viewed by 2213
Abstract
The molecular analysis of circulating analytes (circulating tumor-DNA (ctDNA), -cells (CTCs) and -RNA (ctRNA)/exosomes) deriving from solid tumors and detected in the bloodstream—referred as liquid biopsy—has emerged as one of the most promising concepts in cancer management. Compelling data have evidenced its pivotal [...] Read more.
The molecular analysis of circulating analytes (circulating tumor-DNA (ctDNA), -cells (CTCs) and -RNA (ctRNA)/exosomes) deriving from solid tumors and detected in the bloodstream—referred as liquid biopsy—has emerged as one of the most promising concepts in cancer management. Compelling data have evidenced its pivotal contribution and unique polyvalence through multiple applications. These data essentially derived from translational research. Therewith, data on liquid biopsy in basic research with preclinical models are scarce, a concerning lack that has been widely acknowledged in the field. This report aimed to comprehensively review the available data on the topic, for each analyte. Only 17, 17 and 2 studies in basic research investigated ctDNA, CTCs and ctRNA/exosomes, respectively. Albeit rare, these studies displayed noteworthy relevance, demonstrating the capacity to investigate questions related to the biology underlying analytes release that could not be explored via translational research with human samples. Translational, clinical and technological sectors of liquid biopsy may benefit from basic research and should take note of some important findings generated by these studies. Overall, results underscored the need to intensify the efforts to conduct future studies on liquid biopsy in basic research with new preclinical models. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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25 pages, 2347 KiB  
Review
Circulating Tumor DNA in Precision Oncology and Its Applications in Colorectal Cancer
by Maria F. Arisi, Efrat Dotan and Sandra V. Fernandez
Int. J. Mol. Sci. 2022, 23(8), 4441; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084441 - 18 Apr 2022
Cited by 29 | Viewed by 7472
Abstract
Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that is shed by malignant tumors into the bloodstream and other bodily fluids. ctDNA can comprise up to 10% of a patient’s cfDNA depending on their tumor type and burden. The short [...] Read more.
Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that is shed by malignant tumors into the bloodstream and other bodily fluids. ctDNA can comprise up to 10% of a patient’s cfDNA depending on their tumor type and burden. The short half-life of ctDNA ensures that its detection captures tumor burden in real-time and offers a non-invasive method of repeatedly evaluating the genomic profile of a patient’s tumor. A challenge in ctDNA detection includes clonal hematopoiesis of indeterminate potential (CHIP), which can be distinguished from tumor variants using a paired whole-blood control. Most assays for ctDNA quantification rely on measurements of somatic variant allele frequency (VAF), which is a mutation-dependent method. Patients with certain types of solid tumors, including colorectal cancer (CRC), can have levels of cfDNA 50 times higher than healthy patients. ctDNA undergoes a precipitous drop shortly after tumor resection and therapy, and rising levels can foreshadow radiologic recurrence on the order of months. The amount of tumor bulk required for ctDNA detection is lower than that for computed tomography (CT) scan detection, with ctDNA detection preceding radiologic recurrence in many cases. cfDNA/ctDNA can be used for tumor molecular profiling to identify resistance mutations when tumor biopsy is not available, to detect minimal residual disease (MRD), to monitor therapy response, and for the detection of tumor relapse. Although ctDNA is not yet implemented in clinical practice, studies are ongoing to define the appropriate way to use it as a tool in the clinic. In this review article, we examine the general aspects of ctDNA, its status as a biomarker, and its role in the management of early (II–III) and late (IV; mCRC) stage colorectal cancer (CRC). Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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11 pages, 1332 KiB  
Case Report
Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report
by Carlos Casas-Arozamena, Alexandra Cortegoso, Raquel Piñeiro-Perez, Alicia Abalo, Efigenia Arias, Victoria Sampayo, Ana Vilar, Marta Bouso, Eva Diaz, Gema Moreno-Bueno, Rafael López-López, Laura Muinelo-Romay, Miguel Abal and Juan Cueva
Int. J. Mol. Sci. 2022, 23(15), 8539; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158539 - 01 Aug 2022
Cited by 2 | Viewed by 2393
Abstract
Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being [...] Read more.
Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies. Full article
(This article belongs to the Special Issue Liquid Biopsies in Oncology)
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