scholarly journals Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 349
Author(s):  
Ivana Martins ◽  
Ilda Patrícia Ribeiro ◽  
Joana Jorge ◽  
Ana Cristina Gonçalves ◽  
Ana Bela Sarmento-Ribeiro ◽  
...  
Keyword(s):  
Residual Disease ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Management Tool ◽  
Liquid Biopsies ◽  
Disease Evolution ◽  
Non Invasive ◽  
Routine Clinical Setting ◽  
Tumor Types ◽  
Near Future

The minimally—or non-invasive detection of circulating tumor-derived components in biofluids, such as blood, liquid biopsy is a revolutionary approach with significant potential for the management of cancer. Genomic and transcriptomic alterations can be accurately detected through liquid biopsies, which provide a more comprehensive characterization of the heterogeneous tumor profile than tissue biopsies alone. Liquid biopsies could assist diagnosis, prognosis, and treatment selection, and hold great potential to complement current surveilling strategies to monitor disease evolution and treatment response in real-time. In particular, these are able to detect minimal residual disease, to predict progression, and to identify mechanisms of resistance, allowing to re-orient treatment strategies in a timelier manner. In this review we gathered current knowledge regarding the role and potential of liquid biopsies for the diagnosis and follow-up of cancer patients. The presented findings emphasize the strengths of liquid biopsies, revealing their chance of improving the diagnosis and monitoring of several tumor types in the near future. However, despite growing evidence supporting their value as a management tool in oncology, some limitations still need to be overcome for their implementation in the routine clinical setting.

scholarly journals The microenvironment in mature B-cell malignancies: a target for new treatment strategies

Blood ◽  
2009 ◽  
Vol 114 (16) ◽  
pp. 3367-3375 ◽  
Author(s):  
Jan A. Burger ◽  
Paolo Ghia ◽  
Andreas Rosenwald ◽  
Federico Caligaris-Cappio
Keyword(s):  
B Cell ◽  
Residual Disease ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
B Cell Malignancies ◽  
Accessory Cells ◽  
Specialized Tissue ◽  
New Treatment ◽  
Novel Strategy ◽  
Secondary Lymphoid Organs

AbstractDespite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts.

scholarly journals Y RNA: An Overview of Their Role as Potential Biomarkers and Molecular Targets in Human Cancers

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1238 ◽  
Author(s):  
Caterina Gulìa ◽  
Fabrizio Signore ◽  
Marco Gaffi ◽  
Silvia Gigli ◽  
Raffaella Votino ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Current Knowledge ◽  
Non Invasive ◽  
Bodily Fluids ◽  
Oncological Patients ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Established Role ◽  
Inhibit Cell Proliferation

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients.

scholarly journals Current Treatment Options for Cystic Fibrosis-Related Liver Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8586 ◽  
Author(s):  
Katharina Staufer
Keyword(s):  
Cystic Fibrosis ◽  
Liver Disease ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Transmembrane Conductance Regulator ◽  
Definition Of ◽  
Related Liver Disease ◽  
Near Future

Cystic Fibrosis-related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF), and affects children and adults. The understanding of the pathogenesis of CFLD is key in order to develop efficacious treatments. However, it remains complex, and has not been clarified to the last. The search for a drug might be additionally complicated due to the diverse clinical picture and lack of a unified definition of CFLD. Although ursodeoxycholic acid has been used for decades, its efficacy in CFLD is controversial, and the potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators and targeted gene therapy in CFLD needs to be defined in the near future. This review focuses on the current knowledge on treatment strategies for CFLD based on pathomechanistic viewpoints.

scholarly journals Liver Fibrosis: Causes and Methods of Assessment, A Review

2015 ◽  
Vol 53 (4) ◽  
pp. 304-314 ◽  
Author(s):  
Ali Erfani Karimzadeh Toosi
Keyword(s):  
Liver Fibrosis ◽  
Liver Biopsy ◽  
Hepatic Dysfunction ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Future Research ◽  
Progressive Development ◽  
Non Invasive ◽  
The Past ◽  
Invasive Method

AbstractHepatic fibrogenesis is the final result of injury to the liver. Fibrosis could lead to hepatic dysfunction, important in the pathogenesis of other chronic problems. Therefore, understanding the mechanism, accurate diagnosis and staging of it in early stages accelerates the treatment and reduces the prevalence of chirrosis. Treatment strategies of liver problems and detction methods depend on the amount and progression of liver fibrosis and the rate of cirrhosis development. Traditionally the invasive method, liver biopsy, is reference standard to follow progression and stage of fibrosis. However, during the past decade, progressive development of novel non-invasive methodologies has challenged the invasive method. Non-invasive methods have been initially introduced for chronic hepatitis C with increasing use in other chronic liver diseases. The need for liver biopsy has nowadays decreased significantly as a result of these methodologies. Most of the new non-invasive methods depend on either ‘biological’ or ‘physical’ approaches.In this review, starting from the mechanism of fibrogenesis, the current knowledge about diagnosis, treatment strategies and different methods for its evaluation is discussed. This is followed by a conclusion on what is expected to be known in this field during the future research.

Total microfluidic platform strategy for liquid biopsy

2020 ◽  
pp. 1-25
Author(s):  
Sehyun Shin
Keyword(s):  
Liquid Biopsy ◽  
Residual Disease ◽  
Future Research ◽  
Microfluidic Platforms ◽  
Liquid Biopsies ◽  
Related Area ◽  
Detailed Review ◽  
Non Invasive ◽  
Clinical Benefits ◽  
Minimal Residual

A liquid biopsy is a simple and non-invasive biopsy that examines a range of information about a tumor through a simple blood sample. Due to its non-invasive nature, liquid biopsy has many outstanding clinical benefits, including repetitive sampling and examination, representation of whole mutations, observation of minimal residual disease etc. However, liquid biopsy requires various processes such as sample preparation, amplification, and target detection. These processes can be integrated onto microfluidic platforms, which may provide a sample-to-answer system. The present review provides a brief overview of liquid biopsies, a detailed review of the technologies in each process, and prospective concluding remarks. Through this review, one can have a basic but cross-disciplinary understanding of liquid biopsy, as well as knowledge of new starting points for future research in each related area.

scholarly journals Is Circulating DNA and Tumor Cells in Myeloma the Way Forward?

Hemato ◽  
2022 ◽  
Vol 3 (1) ◽  
pp. 63-81
Author(s):  
Emilie Arnault Carneiro ◽  
Filipa Barahona ◽  
Carolina Pestana ◽  
Cristina João
Keyword(s):  
Tumor Cells ◽  
Peripheral Blood ◽  
Therapeutic Strategy ◽  
Residual Disease ◽  
Scientific Evidence ◽  
Disease Status ◽  
Liquid Biopsies ◽  
Hematological Cancer ◽  
Non Invasive ◽  
Disease Prognosis

Multiple myeloma (MM) is the second deadliest hematological cancer. Despite the enormous innovation on MM treatment in the last decades, still 48% of patients die within 5 years after diagnosis. MM diagnosis and therapeutic strategy mainly rely on direct bone marrow (BM) assessment. Given the MM heterogeneity, BM biopsies do not accurately reflect the whole disease status, hampering accurate disease prognosis. Moreover, biopsies are painful and invasive procedures, highlighting the need for non-invasive and more accurate source of biomarkers. Liquid biopsies are promising sources of biomarkers that may overcome these limitations. Peripheral blood carries circulating myeloma components that are being extensively explored since the last few years as an alternative to BM aspirates. These include circulating tumor cells (CTC), cell-free DNA (cfDNA), and extracellular vesicles containing miRNA and proteins. The current review summarizes scientific evidence establishing BM as a gold standard for the diagnosis, prognosis, and evaluation of minimal residual disease. We discuss the last advances regarding cfDNA and CTC biomarkers from peripheral blood in patients with MM as well as the statistical validations. This paper addresses the technological hurdles associated with liquid biopsies and examines the missing steps for their inclusion into the clinical practice.

scholarly journals Multiple Myeloma: Molecular Pathogenesis and Disease Evolution

2021 ◽  
pp. 1-8
Author(s):  
Michael Heider ◽  
Katharina Nickel ◽  
Marion Högner ◽  
Florian Bassermann
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Current Knowledge ◽  
Hematologic Malignancy ◽  
Clonal Evolution ◽  
Proteasome Inhibitors ◽  
Treatment Strategies ◽  
Disease Evolution ◽  
Oncogenic Pathways

<b><i>Background:</i></b> Multiple myeloma is the second most common hematologic malignancy, which to date remains incurable despite advances in treatment strategies including the use of novel substances such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. <b><i>Summary:</i></b> The bone marrow-based disease is preceded by the 2 sequential premalignant conditions: monoclonal gammo­pathy of undetermined significance and smoldering myeloma. Plasma cell leukemia and extramedullary disease occur, when malignant clones lose their dependency on the bone marrow. Key genetic features of these plasma cell dyscrasias include chromosomal aberrations such as translocations and hyperdiploidy, which occur during error-prone physiologic processes in B-cell development. Next-generation sequencing studies have identified mutations in major oncogenic pathways and tumor suppressors, which contribute to the pathogenesis of multiple myeloma and have revealed insights into the clonal evolution of the disease, particularly along different lines of therapy. More recently, the importance of epigenetic alterations and the role of the bone marrow microenvironment, including immune and osteogenic cells, have become evident. <b><i>Key Messages:</i></b> We herein review the current knowledge of the pathogenesis of multiple myeloma, which is crucial for the development of novel targeted therapeutic strategies. These can contribute to the endeavor to make multiple myeloma a curable disease.

scholarly journals Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 331 ◽  
Author(s):  
Dimple Chudasama ◽  
Periklis Katopodis ◽  
Nick Stone ◽  
Jennifer Haskell ◽  
Hannah Sheridan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Full Potential ◽  
Rna Seq ◽  
Liquid Biopsies ◽  
Promising Alternative ◽  
Disease Evolution ◽  
Blood Samples ◽  
Non Invasive

Background: Liquid biopsies offer a promising alternative to tissue samples, providing non-invasive diagnostic approaches or serial monitoring of disease evolution. However, certain challenges remain, and the full potential of liquid biopsies has yet to be reached. Here we report several methodological approaches to interrogate liquid biopsies using circulating tumour cell (CTC) enumeration and characterisation, transcriptomics, Raman spectroscopy, and copy number instability (CNI) scores using blood samples of lung cancer (LC) patients. Methods: We choose LC; since it still is the most common cause of cancer-related mortality worldwide, and therefore there is a need for development of new non-invasive diagnostic/prognostic technologies. Changes in gene expression were assessed using RNA-seq, and in CTCs using ImageStream, an imaging flow-cytometer. CNI scores, from paired tissue/ctDNA were also explored. Raman spectroscopy was used to provide chemical fingerprints of plasma samples. Results: CTCs were detected in all LC patients (n = 10). We observed a significant increase in CTC levels in LC patients (n = 10) compared to controls (n = 21). A similar CNI was noted in the tissue and plasma of 2 patients, where higher CNI scores corresponded with poorer outcome. Significant changes in Raman spectra (carotenoid concentrations) were noted in LC patients (n = 20) compared to controls (n = 10). RNA-seq revealed differential expression of 21 genes between LC cases and controls in both LC tissue and blood samples. Conclusions: Liquid biopsies can potentially provide a more comprehensive picture of the disease compared to a single tissue biopsy. CTC enumeration is feasible and sensitive for LC patients. Molecular profiling of CTCs is also possible from total blood. CNI scores and Raman spectra require further investigation. Further work is being undertaken to explore these methods of detection in a larger LC cohort.

scholarly journals The pitfalls and promise of liquid biopsies for diagnosing and treating solid tumors in children: a review

2020 ◽  
Vol 179 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Ruben Van Paemel ◽  
Roos Vlug ◽  
Katleen De Preter ◽  
Nadine Van Roy ◽  
Frank Speleman ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Therapy Response ◽  
Response Monitoring ◽  
Liquid Biopsies ◽  
Cell Free Dna ◽  
Pediatric Solid Tumors ◽  
Free Dna ◽  
Tumor Types

AbstractCell-free DNA profiling using patient blood is emerging as a non-invasive complementary technique for cancer genomic characterization. Since these liquid biopsies will soon be integrated into clinical trial protocols for pediatric cancer treatment, clinicians should be informed about potential applications and advantages but also weaknesses and potential pitfalls. Small retrospective studies comparing genetic alterations detected in liquid biopsies with tumor biopsies for pediatric solid tumor types are encouraging. Molecular detection of tumor markers in cell-free DNA could be used for earlier therapy response monitoring and residual disease detection as well as enabling detection of pathognomonic and therapeutically relevant genomic alterations.Conclusion: Existing analyses of liquid biopsies from children with solid tumors increasingly suggest a potential relevance for molecular diagnostics, prognostic assessment, and therapeutic decision-making. Gaps remain in the types of tumors studied and value of detection methods applied. Here we review the current stand of liquid biopsy studies for pediatric solid tumors with a dedicated focus on cell-free DNA analysis. There is legitimate hope that integrating fully validated liquid biopsy–based innovations into the standard of care will advance patient monitoring and personalized treatment of children battling solid cancers. What is Known:• Liquid biopsies are finding their way into routine oncological screening, diagnosis, and disease monitoring in adult cancer types fast.• The most widely adopted source for liquid biopsies is blood although other easily accessible body fluids, such as saliva, pleural effusions, urine, or cerebrospinal fluid (CSF) can also serve as sources for liquid biopsies What is New:• Retrospective proof-of-concept studies in small cohorts illustrate that liquid biopsies in pediatric solid tumors yield tremendous potential to be used in diagnostics, for therapy response monitoring and in residual disease detection.• Liquid biopsy diagnostics could tackle some long-standing issues in the pediatric oncology field; they can enable accurate genetic diagnostics in previously unbiopsied tumor types like renal tumors or brain stem tumors leading to better treatment strategies

Liquid biopsies to enable non-invasive real-time functional chemoresistance profiling in solid organ cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3525-3525
Author(s):  
Dadasaheb B Akolkar ◽  
Timothy Crook ◽  
Raymond Page ◽  
Darshana Patil ◽  
Sewanti Limaye ◽  
...  
Keyword(s):  
Real Time ◽  
Anticancer Agents ◽  
Tumor Tissue ◽  
Checkpoint Inhibitors ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Solid Organ ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Pretreated Patients

3525 Background: Despite the development of targeted therapy agents and immune checkpoint inhibitors (ICI), cytotoxic anticancer agents remain the mainstay of treatment in several solid organ cancers. However, instances of innate and acquired resistance towards these anticancer agents can lead to treatment failures, which remain undetectable until clinical or radiological manifestation of symptoms suggestive of disease progression. There are presently no viable means or markers to detect or monitor for chemoresistance in real time. Owing to this unmet need, cancer treatment strategies face risks of failure and poor outcomes. Methods: We obtained 15 mL blood from 3,662 patients with various solid organ cancers, of various states and including treatment-naïve and pretreated patients. Circulating Tumor Associated Cells (C-TACs) were enriched and harvested from PBMCs using an epigenetically activating medium that is cytotoxic towards non-malignant epithelial and hematolymphoid cells in blood, but confers survival benefit on apoptosis resistant cells of tumorigenic origin (Circulating Tumor Associated Cells, C-TACs). In a subset of patients, fresh tumor tissue was also obtained from which viable tumor derived cells (TDCs) were obtained. Viable TDCs and C-TACs were treated with a panel of anticancer agents and the surviving cell fraction estimated to determine chemoresistance. Results: Among the 1,325 therapy naïve patients, resistance towards treatment agents was observed in C-TACs from 56.3 % of samples. Among 2,201 pretreated patients’ samples, resistance towards treatment agents was observed in C-TACs from 77.8% of samples. The increased resistance in C-TACs from pretreated patients indicated that the C-TACs had been resistance-educated by prior therapies. In a subset of patients, Chemoresistance profile of C-TACs was observed to be 96.9% concordant with that of tumor derived cells (TDCs) which were concurrently obtained from tumor tissue indicating that C-TACs accurately represent chemo-antecedents of the tumor. Conclusions: Non-invasive chemoresistance profiling of C-TACs is a viable strategy to monitor treatment efficacy in real time. Adoption of this strategy in the clinic will not only guide treatment selection with reduced risk of failure, but will also enable timely therapeutic course correction upon detection of acquired chemoresistance.

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