scholarly journals Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Aitor Rodriguez-Casanova ◽  
Nicolás Costa-Fraga ◽  
Aida Bao-Caamano ◽  
Rafael López-López ◽  
Laura Muinelo-Romay ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Current Knowledge ◽  
Monitoring And Evaluation ◽  
Precision Oncology ◽  
Epigenetic Mechanisms ◽  
Epigenetic Alterations ◽  
Liquid Biopsies ◽  
Dna And Rna

Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.

scholarly journals Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4803
Author(s):  
Satoshi Nagayama ◽  
Siew-Kee Low ◽  
Kazuma Kiyotani ◽  
Yusuke Nakamura
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Point Of View ◽  
Liquid Biopsies ◽  
Cell Therapies ◽  
Technological Advances ◽  
Diagnostic Modalities ◽  
Tumor Genome

In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests—‘liquid biopsies’. From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.

scholarly journals Rationale for Early Detection of EWSR1 Translocation-Associated Sarcoma Biomarkers in Liquid Biopsy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 824
Author(s):  
Felix I. L. Clanchy
Keyword(s):  
Early Detection ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Surgical Excision ◽  
Molecular Techniques ◽  
Rt Pcr ◽  
Liquid Biopsies ◽  
Societal Burden ◽  
Recent Developments ◽  
Mesenchymal Tumours

Sarcomas are mesenchymal tumours that often arise and develop as a result of chromosomal translocations, and for several forms of sarcoma the EWSR1 gene is a frequent translocation partner. Sarcomas are a rare form of malignancy, which arguably have a proportionally greater societal burden that their prevalence would suggest, as they are more common in young people, with survivors prone to lifelong disability. For most forms of sarcoma, histological diagnosis is confirmed by molecular techniques such as FISH or RT-PCR. Surveillance after surgical excision, or ablation by radiation or chemotherapy, has remained relatively unchanged for decades, but recent developments in molecular biology have accelerated the progress towards routine analysis of liquid biopsies of peripheral blood. The potential to detect evidence of residual disease or metastasis in the blood has been demonstrated by several groups but remains unrealized as a routine diagnostic for relapse during remission, for disease monitoring during treatment, and for the detection of occult, residual disease at the end of therapy. An update is provided on research relevant to the improvement of the early detection of relapse in sarcomas with EWSR1-associated translocations, in the contexts of biology, diagnosis, and liquid biopsy.

scholarly journals Delivering on the promise of early detection with liquid biopsies

2022 ◽  
Author(s):  
David Crosby
Keyword(s):  
Cancer Research ◽  
Cancer Therapy ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Therapy Monitoring ◽  
Disease Relapse ◽  
Liquid Biopsies ◽  
Cancer Early Detection ◽  
Ideal Position

AbstractLiquid biopsy approaches are relatively well developed for cancer therapy monitoring and disease relapse, but they also have incredible potential in the cancer early detection and screening field. There are, however, several challenges to overcome before this potential can be met. Research in this area needs to be cohesive and, as a driver of research, Cancer Research UK is in an ideal position to enable this.

scholarly journals Rapid response of stage IV colorectal cancer with APC/TP53/KRAS mutations to FOLFIRI and Bevacizumab combination chemotherapy: a case report of use of liquid biopsy

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alexander Hendricks ◽  
Philip Rosenstiel ◽  
Sebastian Hinz ◽  
Greta Burmeister ◽  
Christoph Röcken ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Response ◽  
Liquid Biopsy ◽  
Metastatic Cancer ◽  
Stage Iv ◽  
Liquid Biopsies ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Stage Iv Colorectal Cancer ◽  
Free Dna

Abstract Background Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients. Case presentation In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle, CT imaging, CEA and CA19–9 markers validated the cfDNA findings of treatment response. However, 5 weeks later, the tumour had rapidly progressed. Conclusion As FOLFIRI+Bevacizumab has recently also been associated with sustained complete remission in a APC/TP53/KRAS triple-mutated patient, these driver genes should be tested and monitored in a more in-depth manner in future patients. Patients with metastatic disease should be monitored more closely during and after chemotherapy, ideally using cfDNA.

scholarly journals Genomic Alterations and Their Implications on Survival in Nonmetastatic Colorectal Cancer: Status Quo and Future Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2001 ◽  
Author(s):  
Reetu Mukherji ◽  
John Marshall ◽  
Andreas Seeber
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Daily Routine ◽  
Precision Oncology ◽  
Genomic Alterations ◽  
Future Challenges ◽  
The Status ◽  
Selection Of

The selection of treatment according to genomic alterations is a standard approach in metastatic colorectal cancer but is only starting to have an impact in the earlier stages of the disease. The status of genes like KRAS, BRAF, and MMR has substantial survival implications, and concerted research efforts have revolutionized treatment towards precision oncology. In contrast, a genomic-based approach has not changed the adjuvant setting after curative tumor-resection in the daily routine so far. This review focuses on the current knowledge regarding prognostic and predictive genomic biomarkers in patients with locally advanced nonmetastasized colorectal cancer. Furthermore, we provide an outlook on future challenges for a personalized adjuvant treatment approach in patients with colorectal cancer.

scholarly journals Promising Colorectal Cancer Biomarkers for Precision Prevention and Therapy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1932 ◽  
Author(s):  
Mimmo Turano ◽  
Paolo Delrio ◽  
Daniela Rega ◽  
Francesca Cammarota ◽  
Alessia Polverino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Correct Diagnosis ◽  
Cancer Biomarkers ◽  
Diagnostic Techniques ◽  
Liquid Biopsies ◽  
Tumor Tissues ◽  
Precision Therapy ◽  
Clinical Strategy

Colorectal cancer (CRC) has been ranked as the third most prevalent cancer worldwide. Indeed, it represents 10.2% of all cancer cases. It is also the second most common cause of cancer mortality, and accounted for about 9.2% of all cancer deaths in 2018. Early detection together with a correct diagnosis and staging remains the most effective clinical strategy in terms of disease recovery. Thanks to advances in diagnostic techniques, and improvements of surgical adjuvant and palliative therapies, the mortality rate of CRC has decreased by more than 20% in the last decade. Cancer biomarkers for the early detection of CRC, its management, treatment and follow-up have contributed to the decrease in CRC mortality. Herein, we provide an overview of molecular biomarkers from tumor tissues and liquid biopsies that are approved for use in the CRC clinical setting for early detection, follow-up, and precision therapy, and of biomarkers that have not yet been officially validated and are, nowadays, under investigation.

scholarly journals The Translational Status of Cancer Liquid Biopsies

2019 ◽  
Author(s):  
Sinisa Bratulic ◽  
Francesco Gatto ◽  
Jens Nielsen
Keyword(s):  
Treatment Outcomes ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Body Fluids ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Biomarker Research ◽  
Successes And Challenges

Abstract Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. This can be achieved by leveraging omics information for accurate molecular characterization of tumors. Tumor tissue biopsies are currently the main source of information for molecular profiling. However, biopsies are invasive and limited in resolving spatiotemporal heterogeneity in tumor tissues. Alternative non-invasive liquid biopsies can exploit patient’s body fluids to access multiple layers of tumor-specific biological information (genomes, epigenomes, transcriptomes, proteomes, metabolomes, circulating tumor cells, and exosomes). Analysis and integration of these large and diverse datasets using statistical and machine learning approaches can yield important insights into tumor biology and lead to discovery of new diagnostic, predictive, and prognostic biomarkers. Translation of these new diagnostic tools into standard clinical practice could transform oncology, as demonstrated by a number of liquid biopsy assays already entering clinical use. In this review, we highlight successes and challenges facing the rapidly evolving field of cancer biomarker research. Lay Summary Precision oncology aims to tailor clinical decisions specifically to patients with the objective of improving treatment outcomes. The discovery of biomarkers for precision oncology has been accelerated by high-throughput experimental and computational methods, which can inform fine-grained characterization of tumors for clinical decision-making. Moreover, advances in the liquid biopsy field allow non-invasive sampling of patient’s body fluids with the aim of analyzing circulating biomarkers, obviating the need for invasive tumor tissue biopsies. In this review, we highlight successes and challenges facing the rapidly evolving field of liquid biopsy cancer biomarker research.

scholarly journals Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5825
Author(s):  
Kate I. Glennon ◽  
Mahafarin Maralani ◽  
Narges Abdian ◽  
Antoine Paccard ◽  
Laura Montermini ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Liquid Biopsy ◽  
Renal Cell ◽  
Somatic Mutations ◽  
Circulating Tumor Dna ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Disease Evolution ◽  
Ctdna Analysis

Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tumor DNA (ctDNA) for such informative somatic mutations (liquid biopsy) is considered an important advance for precision oncology in RCC, allowing to monitor molecular disease evolution in real time. However, our knowledge about the utility of ctDNA analysis in RCC is limited, in part due to the lack of RCC-appropriate assays for ctDNA analysis. Here, by interrogating different blood compartments in xenograft models, we identified plasma cell-free (cf) DNA and extracellular vesicles (ev) DNA enriched for RCC-associated ctDNA. Additionally, we developed sensitive targeted sequencing and bioinformatics workflows capable of detecting somatic mutations in RCC-relevant genes with allele frequencies ≥ 0.5%. Applying this assay to patient-matched tumor and liquid biopsies, we captured tumor mutations in cf- and ev-DNA fractions isolated from the blood, highlighting the potentials of both fractions for ctDNA analysis. Overall, our study presents an RCC-appropriate sequencing assay and workflow for ctDNA analysis and provides a proof of principle as to the feasibility of detecting tumor-specific mutations in liquid biopsy in RCC patients.

Incidence of Androgen Receptor and DNA Repair Gene Mutations in Advanced Solid Malignancies: Clinical Impact of Liquid Biopsy at Veteran Affairs Medical Center

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S145-S146
Author(s):  
S Dalal ◽  
D Jhala
Keyword(s):  
Dna Repair ◽  
Liquid Biopsy ◽  
Medical Center ◽  
Gene Mutations ◽  
Genetic Mutations ◽  
Precision Oncology ◽  
Liquid Biopsies ◽  
Repair Gene ◽  
Solid Malignancies ◽  
Dna Repair Gene

Abstract Introduction/Objective The advent of Liquid biopsy targeting genetic mutations in solid tumors is a major milestone in field of precision oncology. This minimally invasive, novel revolutionary technique analyses circulating tumor cells (CTC) in peripheral blood and detects signature genomic alterations. DNA repair gene (DDR) mutations have been reported in 25-40% of prostatic cancers and >50% of non-small cell lung cancers (NSCLC), being more common in late-stage and hormone refractory prostate cancers. One of the DDR, especially Tp53 has been found to be associated with poor prognosis and increased germline mutations. We herein present a quality assurance study to determine feasibility of liquid biopsy for personalized management in veterans for advanced solid malignancies and its clinical impact. Methods Quality assurance documentation from Foundation One (Cambridge MA, NGS) on liquid biopsies performed for the Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMCVAMC) from May 2019 to April 15, 2020 were reviewed. Statistical data for adequacy, cases with notable mutations, frequency and type of mutations of AR, DNA damage repair (DDR) gene and Tp53 were noted. Results A total of 31 liquid biopsies were performed over this time period, of which 29/31 (93.50%) were adequate for evaluation. 23/29 (79.30%) showed notable mutations, in 4/23 (17.39%) guided treatment decisions based on androgen receptor (AR) amplification, and 7/29 (24.1%) of all cases showed DDR gene mutations indicating poor outcome and resistance to the current therapy. Greater than 50% (16/29 (55.7%)) of the veterans with advanced cancers harbored Tp53 mutation, which instills hope and future insight for patient tailored oncologic therapy. Conclusion The minimally invasive liquid biopsy shows a great promise as a diagnostic and prognostic tool in the personalized clinical management of advanced prostate and NSCLC in veteran patient population with unique demographic characteristics. Difference in frequency of the genetic mutations (DDR, TP53, AR) in this cohort provides valuable information for disease progression, lack of response, mechanism of resistance to the implemented therapy and clinical decision making. Precision oncology can be further tailored for this cohort by focusing on DNA repair genes and Tp53 in future for personalized targeted therapy.

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