Biomedicines

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Open AccessEditorial

Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches

by Valeria Barresi

Biomedicines 2021, 9(12), 1858; https://doi.org/10.3390/biomedicines9121858 - 08 Dec 2021

Cited by 6 | Viewed by 3271

Abstract

According to the Global Cancer Statistics 2020, colorectal cancer (CRC) represents the third most frequent malignancy worldwide, and is the second in terms of mortality [...] Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

Research

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28 pages, 8587 KiB

Open AccessArticle

Establishment of a Patient-Derived Xenograft Model of Colorectal Cancer in CIEA NOG Mice and Exploring Smartfish Liquid Diet as a Source of Omega-3 Fatty Acids

by Helle Samdal, Lene C Olsen, Knut S Grøn, Elin S Røyset, Therese S Høiem, Ingunn Nervik, Pål Sætrom, Arne Wibe, Svanhild A Schønberg and Caroline H H Pettersen

Biomedicines 2021, 9(3), 282; https://doi.org/10.3390/biomedicines9030282 - 10 Mar 2021

Cited by 1 | Viewed by 4247

Abstract

Cancer patient-derived xenografts (PDXs) better preserve tumor characteristics and microenvironment than traditional cancer cell line derived xenografts and are becoming a valuable model in translational cancer research and personalized medicine. We have established a PDX model for colorectal cancer (CRC) in CIEA NOG [...] Read more.

Cancer patient-derived xenografts (PDXs) better preserve tumor characteristics and microenvironment than traditional cancer cell line derived xenografts and are becoming a valuable model in translational cancer research and personalized medicine. We have established a PDX model for colorectal cancer (CRC) in CIEA NOG mice with a 50% engraftment rate. Tumor fragments from patients with CRC (n = 5) were engrafted in four mice per tumor (n = 20). Mice with established PDXs received a liquid diet enriched with fish oil or placebo, and fatty acid profiling was performed to measure fatty acid content in whole blood. Moreover, a biobank consisting of tissue and blood samples from patients was established. Histology, immunohistochemistry and in situ hybridization procedures were used for staining of tumor and xenograft tissue slides. Results demonstrate that key histological characteristics of the patients’ tumors were retained in the established PDXs, and the liquid diets were consumed as intended by the mice. Some of the older mice developed lymphomas that originated from human Ki67⁺, CD45⁺, and EBV⁺ lymphoid cells. We present a detailed description of the process and methodology, as well as possible issues that may arise, to refine the method and improve PDX engraftment rate for future studies. The established PDX model for CRC can be used for exploring different cancer treatment regimes, and liquid diets enriched with fish oil may be successfully delivered to the mice through the drinking flasks. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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22 pages, 4150 KiB

Open AccessArticle

Identification and Validation of New Cancer Stem Cell-Related Genes and Their Regulatory microRNAs in Colorectal Cancerogenesis

by Kristian Urh, Margareta Žlajpah, Nina Zidar and Emanuela Boštjančič

Biomedicines 2021, 9(2), 179; https://doi.org/10.3390/biomedicines9020179 - 11 Feb 2021

Cited by 12 | Viewed by 2202

Abstract

Significant progress has been made in the last decade in our understanding of the pathogenetic mechanisms of colorectal cancer (CRC). Cancer stem cells (CSC) have gained much attention and are now believed to play a crucial role in the pathogenesis of various cancers, [...] Read more.

Significant progress has been made in the last decade in our understanding of the pathogenetic mechanisms of colorectal cancer (CRC). Cancer stem cells (CSC) have gained much attention and are now believed to play a crucial role in the pathogenesis of various cancers, including CRC. In the current study, we validated gene expression of four genes related to CSC, L1TD1, SLITRK6, ST6GALNAC1 and TCEA3, identified in a previous bioinformatics analysis. Using bioinformatics, potential miRNA-target gene correlations were prioritized. In total, 70 formalin-fixed paraffin-embedded biopsy samples from 47 patients with adenoma, adenoma with early carcinoma and CRC without and with lymph node metastases were included. The expression of selected genes and microRNAs (miRNAs) was evaluated using quantitative PCR. Differential expression of all investigated genes and four of six prioritized miRNAs (hsa-miR-199a-3p, hsa-miR-335-5p, hsa-miR-425-5p, hsa-miR-1225-3p, hsa-miR-1233-3p and hsa-miR-1303) was found in at least one group of CRC cancerogenesis. L1TD1, SLITRK6, miR-1233-3p and miR-1225-3p were correlated to the level of malignancy. A negative correlation between miR-199a-3p and its predicted target SLITRK6 was observed, showing potential for further experimental validation in CRC. Our results provide further evidence that CSC-related genes and their regulatory miRNAs are involved in CRC development and progression and suggest that some them, particularly miR-199a-3p and its SLITRK6 target gene, are promising for further validation in CRC. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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18 pages, 5477 KiB

Open AccessArticle

Reinforcement of Colonic Anastomosis with Improved Ultrafine Nanofibrous Patch: Experiment on Pig

by Jachym Rosendorf, Marketa Klicova, Lenka Cervenkova, Jana Horakova, Andrea Klapstova, Petr Hosek, Richard Palek, Jan Sevcik, Robert Polak, Vladislav Treska, Jiri Chvojka and Vaclav Liska

Biomedicines 2021, 9(2), 102; https://doi.org/10.3390/biomedicines9020102 - 21 Jan 2021

Cited by 7 | Viewed by 2494

Abstract

Anastomotic leakage is a dreadful complication in colorectal surgery. It has a negative impact on postoperative mortality, long term life quality and oncological results. Nanofibrous polycaprolactone materials have shown pro-healing properties in various applications before. Our team developed several versions of these for [...] Read more.

Anastomotic leakage is a dreadful complication in colorectal surgery. It has a negative impact on postoperative mortality, long term life quality and oncological results. Nanofibrous polycaprolactone materials have shown pro-healing properties in various applications before. Our team developed several versions of these for healing support of colorectal anastomoses with promising results in previous years. In this study, we developed highly porous biocompatible polycaprolactone nanofibrous patches. We constructed a defective anastomosis on the large intestine of 16 pigs, covered the anastomoses with the patch in 8 animals (Experimental group) and left the rest uncovered (Control group). After 21 days of observation we evaluated postoperative changes, signs of leakage and other complications. The samples were assessed histologically according to standardized protocols. The material was easy to work with. All animals survived with no major complication. There were no differences in intestinal wall integrity between the groups and there were no signs of anastomotic leakage in any animal. The levels of collagen were significantly higher in the Experimental group, which we consider to be an indirect sign of higher mechanical strength. The material shall be further perfected in the future and possibly combined with active molecules to specifically influence the healing process. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 9263 KiB

Open AccessArticle

Clinical Significance of Preoperative Inflammatory Markers in Prediction of Prognosis in Node-Negative Colon Cancer: Correlation between Neutrophil-to-Lymphocyte Ratio and Poorly Differentiated Clusters

by Giulia Turri, Valeria Barresi, Alessandro Valdegamberi, Gabriele Gecchele, Cristian Conti, Serena Ammendola, Alfredo Guglielmi, Aldo Scarpa and Corrado Pedrazzani

Biomedicines 2021, 9(1), 94; https://doi.org/10.3390/biomedicines9010094 - 19 Jan 2021

Cited by 11 | Viewed by 2306

Abstract

Although stage I and II colon cancers (CC) generally show a very good prognosis, a small proportion of these patients dies from recurrent disease. The identification of high-risk patients, who may benefit from adjuvant chemotherapy, becomes therefore essential. We retrospectively evaluated 107 cases [...] Read more.

Although stage I and II colon cancers (CC) generally show a very good prognosis, a small proportion of these patients dies from recurrent disease. The identification of high-risk patients, who may benefit from adjuvant chemotherapy, becomes therefore essential. We retrospectively evaluated 107 cases of stage I (n = 28, 26.2%) and II (n = 79, 73.8%) CC for correlations among preoperative inflammatory markers, histopathological factors and long-term prognosis. A neutrophil-to-lymphocyte ratio greater than 3 (H-NLR) and a platelet-to-lymphocyte ratio greater than 150 (H-PLR) were significantly associated with the presence of poorly differentiated clusters (PDC) (p = 0.007 and p = 0.039, respectively). In addition, H-NLR and PDC proved to be significant and independent survival prognosticators for overall survival (OS; p = 0.007 and p < 0.001, respectively), while PDC was the only significant prognostic factor for cancer-specific survival (CSS; p < 0.001,). Finally, the combination of H-NLR and PDC allowed an optimal stratification of OS and CSS in our cohort, suggesting a potential role in clinical practice for the identification of high-risk patients with stage I and II CC. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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16 pages, 2671 KiB

Open AccessArticle

TCox: Correlation-Based Regularization Applied to Colorectal Cancer Survival Data

by Carolina Peixoto, Marta B. Lopes, Marta Martins, Luís Costa and Susana Vinga

Biomedicines 2020, 8(11), 488; https://doi.org/10.3390/biomedicines8110488 - 10 Nov 2020

Cited by 3 | Viewed by 2988

Abstract

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Being a heterogeneous disease, cancer therapy and prognosis represent a significant challenge to medical care. The molecular information improves the accuracy with which patients are classified and [...] Read more.

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Being a heterogeneous disease, cancer therapy and prognosis represent a significant challenge to medical care. The molecular information improves the accuracy with which patients are classified and treated since similar pathologies may show different clinical outcomes and other responses to treatment. However, the high dimensionality of gene expression data makes the selection of novel genes a problematic task. We propose TCox, a novel penalization function for Cox models, which promotes the selection of genes that have distinct correlation patterns in normal vs. tumor tissues. We compare TCox to other regularized survival models, Elastic Net, HubCox, and OrphanCox. Gene expression and clinical data of CRC and normal (TCGA) patients are used for model evaluation. Each model is tested 100 times. Within a specific run, eighteen of the features selected by TCox are also selected by the other survival regression models tested, therefore undoubtedly being crucial players in the survival of colorectal cancer patients. Moreover, the TCox model exclusively selects genes able to categorize patients into significant risk groups. Our work demonstrates the ability of the proposed weighted regularizer TCox to disclose novel molecular drivers in CRC survival by accounting for correlation-based network information from both tumor and normal tissue. The results presented support the relevance of network information for biomarker identification in high-dimensional gene expression data and foster new directions for the development of network-based feature selection methods in precision oncology. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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16 pages, 1920 KiB

Open AccessArticle

Functional Characterization of Colon-Cancer-Associated Variants in ADAM17 Affecting the Catalytic Domain

by Jan Philipp Dobert, Anne-Sophie Cabron, Philipp Arnold, Egor Pavlenko, Stefan Rose-John and Friederike Zunke

Biomedicines 2020, 8(11), 463; https://doi.org/10.3390/biomedicines8110463 - 30 Oct 2020

Cited by 5 | Viewed by 2164

Abstract

Although extensively investigated, cancer is still one of the most devastating and lethal diseases in the modern world. Among different types, colorectal cancer (CRC) is most prevalent and mortal, making it an important subject of research. The metalloprotease ADAM17 has been implicated in [...] Read more.

Although extensively investigated, cancer is still one of the most devastating and lethal diseases in the modern world. Among different types, colorectal cancer (CRC) is most prevalent and mortal, making it an important subject of research. The metalloprotease ADAM17 has been implicated in the development of CRC due to its involvement in signaling pathways related to inflammation and cell proliferation. ADAM17 is capable of releasing membrane-bound proteins from the cell surface in a process called shedding. A deficiency of ADAM17 activity has been previously shown to have protective effects against CRC in mice, while an upregulation of ADAM17 activity is suspected to facilitate tumor development. In this study, we characterize ADAM17 variants found in tissue samples of cancer patients in overexpression studies. We here focus on point mutations identified within the catalytic domain of ADAM17 and could show a functional dysregulation of the CRC-associated variants. Since the catalytic domain of ADAM17 is the only region structurally determined by crystallography, we study the effect of each point mutation not only to learn more about the role of ADAM17 in cancer, but also to investigate the structure–function relationships of the metalloprotease. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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11 pages, 2901 KiB

Open AccessArticle

MSH2 Overexpression Due to an Unclassified Variant in 3’-Untranslated Region in a Patient with Colon Cancer

by Raffaella Liccardo, Antonio Nolano, Matilde Lambiase, Carlo Della Ragione, Marina De Rosa, Paola Izzo and Francesca Duraturo

Biomedicines 2020, 8(6), 167; https://doi.org/10.3390/biomedicines8060167 - 19 Jun 2020

Cited by 7 | Viewed by 2548

Abstract

Background: The loss or low expression of DNA mismatch repair (MMR) genes can result in genomic instability and tumorigenesis. One such gene, MSH2, is mutated or rearranged in Lynch syndrome (LS), which is characterized by a high risk of tumor development, including colorectal [...] Read more.

Background: The loss or low expression of DNA mismatch repair (MMR) genes can result in genomic instability and tumorigenesis. One such gene, MSH2, is mutated or rearranged in Lynch syndrome (LS), which is characterized by a high risk of tumor development, including colorectal cancer. However, many variants identified in this gene are often defined as variants of uncertain significance (VUS). In this study, we selected a variant in the 3′ untranslated region (UTR) of MSH2 (c*226A > G), identified in three affected members of a LS family and already reported in the literature as a VUS. Methods: The effect of this variant on the activity of the MMR complex was examined using a set of functional assays to evaluate MSH2 expression. Results: We found MSH2 was overexpressed compared to healthy controls, as determined by RTqPCR and Western blot analyses of total RNA and proteins, respectively, extracted from peripheral blood samples. These results were confirmed by luciferase reporter gene assays. Conclusions: We therefore speculated that, in addition to canonical inactivation via a gene mutation, MMR activity may also be modulated by changes in MMR gene expression. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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Review

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20 pages, 475 KiB

Open AccessReview

TRIM Proteins in Colorectal Cancer: TRIM8 as a Promising Therapeutic Target in Chemo Resistance

by Flaviana Marzano, Mariano Francesco Caratozzolo, Graziano Pesole, Elisabetta Sbisà and Apollonia Tullo

Biomedicines 2021, 9(3), 241; https://doi.org/10.3390/biomedicines9030241 - 27 Feb 2021

Cited by 12 | Viewed by 2520

Abstract

Colorectal cancer (CRC) represents one of the most widespread forms of cancer in the population and, as all malignant tumors, often develops resistance to chemotherapies with consequent tumor growth and spreading leading to the patient’s premature death. For this reason, a great challenge [...] Read more.

Colorectal cancer (CRC) represents one of the most widespread forms of cancer in the population and, as all malignant tumors, often develops resistance to chemotherapies with consequent tumor growth and spreading leading to the patient’s premature death. For this reason, a great challenge is to identify new therapeutic targets, able to restore the drugs sensitivity of cancer cells. In this review, we discuss the role of TRIpartite Motifs (TRIM) proteins in cancers and in CRC chemoresistance, focusing on the tumor-suppressor role of TRIM8 protein in the reactivation of the CRC cells sensitivity to drugs currently used in the clinical practice. Since the restoration of TRIM8 protein levels in CRC cells recovers chemotherapy response, it may represent a new promising therapeutic target in the treatment of CRC. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

29 pages, 1692 KiB

Open AccessReview

What Is Known about Theragnostic Strategies in Colorectal Cancer

by Alessandro Parisi, Giampiero Porzio, Fanny Pulcini, Katia Cannita, Corrado Ficorella, Vincenzo Mattei and Simona Delle Monache

Biomedicines 2021, 9(2), 140; https://doi.org/10.3390/biomedicines9020140 - 01 Feb 2021

Cited by 8 | Viewed by 3311

Abstract

Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both [...] Read more.

Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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24 pages, 2665 KiB

Open AccessReview

Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers

by Kyusang Hwang, Jin Hwan Yoon, Ji Hyun Lee and Sukmook Lee

Biomedicines 2021, 9(1), 39; https://doi.org/10.3390/biomedicines9010039 - 05 Jan 2021

Cited by 17 | Viewed by 4094

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Recent advances in recombinant DNA technology have led to the development of numerous therapeutic antibodies as major sources of blockbuster drugs for CRC therapy. Simultaneously, increasing numbers of therapeutic targets [...] Read more.

Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Recent advances in recombinant DNA technology have led to the development of numerous therapeutic antibodies as major sources of blockbuster drugs for CRC therapy. Simultaneously, increasing numbers of therapeutic targets in CRC have been identified. In this review, we first highlight the physiological and pathophysiological roles and signaling mechanisms of currently known and emerging therapeutic targets, including growth factors and their receptors as well as immune checkpoint proteins, in CRC. Additionally, we discuss the current status of monoclonal antibodies in clinical development and approved by US Food and Drug Administration for CRC therapy. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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19 pages, 588 KiB

Open AccessReview

Gut Microbiota and Colorectal Cancer Development: A Closer Look to the Adenoma-Carcinoma Sequence

by Marco Vacante, Roberto Ciuni, Francesco Basile and Antonio Biondi

Biomedicines 2020, 8(11), 489; https://doi.org/10.3390/biomedicines8110489 - 10 Nov 2020

Cited by 50 | Viewed by 5979

Abstract

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or [...] Read more.

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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29 pages, 1538 KiB

Open AccessReview

Genetic Alterations of Metastatic Colorectal Cancer

by Ugo Testa, Germana Castelli and Elvira Pelosi

Biomedicines 2020, 8(10), 414; https://doi.org/10.3390/biomedicines8100414 - 13 Oct 2020

Cited by 28 | Viewed by 4038

Abstract

Genome sequencing studies have characterized the genetic alterations of different tumor types, highlighting the diversity of the molecular processes driving tumor development. Comprehensive sequencing studies have defined molecular subtypes of colorectal cancers (CRCs) through the identification of genetic events associated with microsatellite stability [...] Read more.

Genome sequencing studies have characterized the genetic alterations of different tumor types, highlighting the diversity of the molecular processes driving tumor development. Comprehensive sequencing studies have defined molecular subtypes of colorectal cancers (CRCs) through the identification of genetic events associated with microsatellite stability (MSS), microsatellite-instability-high (MSI-H), and hypermutation. Most of these studies characterized primary tumors. Only recent studies have addressed the characterization of the genetic and clinical heterogeneity of metastatic CRC. Metastatic CRC genomes were found to be not fundamentally different from primary CRCs in terms of the mutational landscape or of genes that drive tumorigenesis, and a genomic heterogeneity associated with tumor location of primary tumors helps to define different clinical behaviors of metastatic CRCs. Although CRC metastatic spreading was traditionally seen as a late-occurring event, growing evidence suggests that this process can begin early during tumor development and the clonal architecture of these tumors is consistently influenced by cancer treatment. Although the survival rate of patients with metastatic CRC patients improved in the last years, the response to current treatments and prognosis of many of these patients remain still poor, indicating the need to discover new improvements for therapeutic vulnerabilities and to formulate a rational prospective of personalized therapies. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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21 pages, 290 KiB

Open AccessReview

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview

by Marco Vacante, Roberto Ciuni, Francesco Basile and Antonio Biondi

Biomedicines 2020, 8(9), 308; https://doi.org/10.3390/biomedicines8090308 - 26 Aug 2020

Cited by 45 | Viewed by 5897

Abstract

Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A “liquid biopsy” is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long [...] Read more.

Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A “liquid biopsy” is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs, and proteins, from peripheral blood or other body fluids and their genomic or proteomic assessment. The liquid biopsy is a minimally invasive and repeatable technique that could play a significant role in screening and diagnosis, and predict relapse and metastasis, as well as monitoring minimal residual disease and chemotherapy resistance in colorectal cancer patients. However, there are still some practical issues that need to be addressed before liquid biopsy can be widely used in clinical practice. Potential challenges may include low amounts of circulating tumor cells and circulating tumor DNA in samples, lack of pre-analytical and analytical consensus, clinical validation, and regulatory endorsement. The aim of this review was to summarize the current knowledge of the role of liquid biopsy in the management of colorectal cancer. Full article

(This article belongs to the Special Issue Colorectal Cancer: From Pathophysiology to Novel Therapeutic Approaches)

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