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Colorectal Cancers: From Present Problems to Future Solutions Volume II

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 20949

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Prof. Dr. Heike Allgayer

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Department of Experimental Surgery - Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University of Heidelberg, 68167 Mannheim, Germany
Interests: cancer metastasis; translational research; tumor-associated proteases; microRNAs; molecular staging; gastrointestinal cancers
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Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous one “Colorectal Cancers: From Present Problems to Future Solutions”.

Colorectal cancer is one of the most frequent cancer entities in humans. The scientific community has made significant progress in our molecular understanding of colorectal carcinogenesis, of hereditary as well as sporadic colorectal cancer types, this pertaining to the discovery of, e.g., (mutated) oncogenes and tumor suppressor genes, microsatellite instabilities, modifications in DNA repair, cellular aging, signaling cascades; genomic, epigenetic, transcriptional, translational, and protein modifications; as well as microbiotic factors and further parameters. Progression and metastasis have been more intensively studied in recent years, leading to an intensified knowledge on molecular protagonists and microenvironmental interactions contributing to invasion, dissemination, and metastasis; still, more concerted efforts need to be made to better understand issues such as metastasis to different sites, or the metastatic heterogeneity of single cells. Nevertheless, based on actual discoveries, personalized medicine, together with highly interdisciplinary therapeutic strategies combining advanced levels of surgical techniques, oncology, and radiation in neoadjuvant, adjuvant, or palliative settings, has started to improve the clinical prognosis of individual patients with colorectal cancer. However, too many patients with this disease will still be diagnosed in too advanced a stage, develop relapse and metastasis despite modern interdisciplinary and personalized therapy advances, and finally die of this disease, which still belongs to the top killer cancer entities in the world.

The present Special Issue will feature articles of different international experts with the latest data in the fields mentioned above. It will include novel hypotheses on molecular drivers of the disease, advanced ideas on cancer cell heterogeneity and its diagnosis, and discussions about the latest model systems and advances in the translation of molecular knowledge into clinical studies. With this Special Issue, we aim to deepen discussions and ideas amongst colleagues in all kinds of disciplines working on this disease, and to intensify translational and interdisciplinary collaborations aimed at an ultimate understanding of strategies to defeat, and prevent, colorectal cancer and its progression.

Prof. Dr. Heike Allgayer
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

colorectal cancer
(molecular) carcinogenesis
progression
metastasis
(single) cancer cell heterogeneity
models
(targeted) therapy
personalized medicine

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Colorectal Cancers: From Present Problems to Future Solutions in Cancers (14 articles)

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19 pages, 2610 KiB

Open AccessArticle

MACC1 Regulates LGR5 to Promote Cancer Stem Cell Properties in Colorectal Cancer

by Müge Erdem, Kyung Hwan Lee, Markus Hardt, Joseph L. Regan, Dennis Kobelt, Wolfgang Walther, Margarita Mokrizkij, Christian Regenbrecht and Ulrike Stein

Cancers 2024, 16(3), 604; https://doi.org/10.3390/cancers16030604 - 31 Jan 2024

Cited by 1 | Viewed by 1277

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. The high mortality is directly associated with metastatic disease, which is thought to be initiated by colon cancer stem cells, according to the cancer stem cell (CSC) model. Consequently, early identification of those patients who are at high risk for metastasis is crucial for improved treatment and patient outcomes. Metastasis-associated in colon cancer 1 (MACC1) is a novel prognostic biomarker for tumor progression and metastasis formation independent of tumor stage. We previously showed an involvement of MACC1 in cancer stemness in the mouse intestine of our MACC1 transgenic mouse models. However, the expression of MACC1 in human CSCs and possible implications remain elusive. Here, we explored the molecular mechanisms by which MACC1 regulates stemness and the CSC-associated invasive phenotype based on patient-derived tumor organoids (PDOs), patient-derived xenografts (PDXs) and human CRC cell lines. We showed that CD44-enriched CSCs from PDO models express significantly higher levels of MACC1 and LGR5 and display higher tumorigenicity in immunocompromised mice. Similarly, RNA sequencing performed on PDO and PDX models demonstrated significantly increased MACC1 expression in ALDH1(+) CSCs, highlighting its involvement in cancer stemness. We further showed the correlation of MACC1 with the CSC markers CD44, NANOG and LGR5 in PDO models as well as established cell lines. Additionally, MACC1 increased stem cell gene expression, clonogenicity and sphere formation. Strikingly, we showed that MACC1 binds as a transcription factor to the LGR5 gene promoter, uncovering the long-known CSC marker LGR5 as a novel essential signaling mediator employed by MACC1 to induce CSC-like properties in human CRC patients. Our in vitro findings were further substantiated by a significant positive correlation of MACC1 with LGR5 in CRC cell lines as well as CRC patient tumors. Taken together, this study indicates that the metastasis inducer MACC1 acts as a cancer stem cell-associated marker. Interventional approaches targeting MACC1 would potentially improve further targeted therapies for colorectal cancer patients to eradicate CSCs and prevent cancer recurrence and distant metastasis formation. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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14 pages, 1137 KiB

Open AccessArticle

Sensitive and Specific Analyses of Colorectal Cancer Recurrence through Multiplex superRCA Mutation Detection in Blood Plasma

by Emma Sandberg, Luís Nunes, Per-Henrik Edqvist, Lucy Mathot, Lei Chen, Tomas Edgren, Shahed Al Nassralla, Bengt Glimelius, Ulf Landegren and Tobias Sjöblom

Cancers 2024, 16(3), 549; https://doi.org/10.3390/cancers16030549 - 27 Jan 2024

Viewed by 1028

Abstract

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10⁻⁵, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10⁻⁴ or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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18 pages, 4607 KiB

Open AccessArticle

CYP26A1 Links WNT and Retinoic Acid Signaling: A Target to Differentiate ALDH+ Stem Cells in APC-Mutant CRC

by Caroline O. B. Facey, Victoria O. Hunsu, Chi Zhang, Brian Osmond, Lynn M. Opdenaker and Bruce M. Boman

Cancers 2024, 16(2), 264; https://doi.org/10.3390/cancers16020264 - 7 Jan 2024

Viewed by 1325

Abstract

APC mutation is the main driving mechanism of CRC development and leads to constitutively activated WNT signaling, overpopulation of ALDH+ stem cells (SCs), and incomplete differentiation. We previously reported that retinoic acid (RA) receptors are selectively expressed in ALDH+ SCs, which provides a way to target cancer SCs with retinoids to induce differentiation. Hypotheses: A functional link exists between the WNT and RA pathways, and APC mutation generates a WNT:RA imbalance that decreases retinoid-induced differentiation and increases ALDH+ SCs. Accordingly, to restore parity in WNT:RA signaling, we induce wt-APC expression in APC-mutant CRC cells, and we assess the ability of all-trans retinoic acid (ATRA) to induce differentiation. We found that ATRA increased expression of the WNT target gene, CYP26A1, and inducing wt-APC reduced this expression by 50%. Thus, the RA and WNT pathways crosstalk to modulate CYP26A1, which metabolizes retinoids. Moreover, inducing wt-APC augments ATRA-induced cell differentiation by: (i) decreasing cell proliferation; (ii) suppressing ALDH1A1 expression; (iii) decreasing ALDH+ SCs; and (iv) increasing neuroendocrine cell differentiation. A novel CYP26A1-based network that links WNT and RA signaling was also identified by NanoString profiling/bioinformatics analysis. Furthermore, CYP26A1 inhibitors sensitized CRC cells to the anti-proliferative effect of drugs that downregulate WNT signaling. Notably, in wt-APC-CRCs, decreased CYP26A1 improved patient survival. These findings have strong potential for clinical translation. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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15 pages, 2284 KiB

Open AccessArticle

Expression Status of Rap1 Pathway-Related Genes in Liver Metastases Compared with Corresponding Primary Colorectal Cancer

by Maryam Abbastabar, Heike Allgayer, Mahdi Sepidarkish, Farzin Sadeghi, Maryam Ghasemi, Roghayeh Pour-bagher and Hadi Parsian

Cancers 2024, 16(1), 171; https://doi.org/10.3390/cancers16010171 - 29 Dec 2023

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Abstract

Understanding molecular networks of CRLM is an ongoing area of research. In this study, paired CRC tissue and adjacent noncancerous tissue from 15 non-metastatic CRC patients and paired CRC tissue and matched liver metastatic tissues from 15 CRLM patients along with their adjacent noncancerous tissues were evaluated. We assessed Rap1 pathway-related genes including NRAS, FGF-1, NGF, and KDR expression by qRT-PCR and their protein status by Western blot. In CRLM patients, NRAS, FGF1, and KDR mRNA and protein were expressed at higher levels in metastatic than in CRC primary tumor and adjacent noncancerous tissue (p < 0.05). In non-metastatic patients, NRAS, FGF1, KDR, and NGF gene expression did not differ between CRC primary tumor-and adjacent noncancerous tissue (p > 0.05). ROC curve analysis showed a reasonable diagnostic accuracy of NRAS, FGF1, KDR, and FGF for the discrimination of metastatic patients from non- metastatic ones on analysis of their primary tumors. The data suggest that further functional studies on Rap1-related genes’ role in CRLM are needed. In conclusion, the present data broaden our knowledge about specific molecular characteristics of CRLM. An increased understanding of the molecular features of metastasis has the potential to create more successful treatment, or prevention, of metastasis, especially in multimodal primary tumor treatment. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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20 pages, 2783 KiB

Open AccessArticle

Commensal Fecal Microbiota Profiles Associated with Initial Stages of Intestinal Mucosa Damage: A Pilot Study

by Sergio Ruiz-Saavedra, Silvia Arboleya, Alicja M. Nogacka, Carmen González del Rey, Adolfo Suárez, Ylenia Diaz, Miguel Gueimonde, Nuria Salazar, Sonia González and Clara G. de los Reyes-Gavilán

Cancers 2024, 16(1), 104; https://doi.org/10.3390/cancers16010104 - 24 Dec 2023

Cited by 1 | Viewed by 1099

Abstract

Progressive intestinal mucosal damage occurs over years prior to colorectal cancer (CRC) development. The endoscopic screening of polyps and histopathological examination are used clinically to determine the risk and progression of mucosal lesions. We analyzed fecal microbiota compositions using 16S rRNA gene-based metataxonomic analyses and the levels of short-chain fatty acids (SCFAs) using gas chromatography in volunteers undergoing colonoscopy and histopathological analyses to determine the microbiota shifts occurring at the early stages of intestinal mucosa alterations. The results were compared between diagnosis groups (nonpathological controls and polyps), between samples from individuals with hyperplastic polyps or conventional adenomas, and between grades of dysplasia in conventional adenomas. Some microbial taxa from the Bacillota and Euryarchaeota phyla were the most affected when comparing the diagnosis and histopathological groups. Deeper microbiota alterations were found in the conventional adenomas than in the hyperplastic polyps. The Ruminococcus torques group was enriched in both the hyperplastic polyps and conventional adenomas, whereas the family Eggerthellaceae was enriched only in the hyperplastic polyps. The abundance of Prevotellaceae, Oscillospiraceae, Methanobacteriaceae, Streptococcaceae, Christensenellaceae, Erysipelotrichaceae, and Clostridiaceae shifted in conventional adenomas depending on the grade of dysplasia, without affecting the major SCFAs. Our results suggest a reorganization of microbial consortia involved in gut fermentative processes. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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12 pages, 537 KiB

Open AccessArticle

Novel Pathogenic Variants in Hereditary Cancer Syndromes in a Highly Heterogeneous Cohort of Patients: Insights from Multigene Analysis

by Airat Bilyalov, Anastasiia Danishevich, Sergey Nikolaev, Nikita Vorobyov, Ivan Abramov, Ekaterina Pismennaya, Svetlana Terehova, Yuliya Kosilova, Anastasiia Primak, Uglesha Stanoevich, Tatyana Lisica, German Shipulin, Sergey Gamayunov, Elena Kolesnikova, Igor Khatkov, Oleg Gusev and Natalia Bodunova

Cancers 2024, 16(1), 85; https://doi.org/10.3390/cancers16010085 - 23 Dec 2023

Viewed by 1056

Abstract

Cancer is a major global public health challenge, affecting both quality of life and mortality. Recent advances in genetic research have uncovered hereditary cancer syndromes (HCS) that predispose individuals to malignant neoplasms. While traditional single-gene testing has focused on high-penetrance genes, the past decade has seen a shift toward multigene panels, which facilitate the analysis of multiple genes associated with specific HCS. This approach reveals variants in less-studied gene regions and improves our understanding of cancer predisposition. In a study composed of Russian patients with clinical signs of HCS, we used a multigene hereditary cancer panel and revealed 21.6% individuals with pathogenic or likely pathogenic genetic variants. BRCA1/BRCA2 mutations predominated, followed by the CHEK2 and ATM variants. Of note, 16 previously undescribed variants were identified in the MUTYH, GALNT12, MSH2, MLH1, MLH3, EPCAM, and POLE genes. The implications of the study extend to personalized cancer prevention and treatment strategies, especially in populations lacking extensive epidemiological data, such as Russia. Overall, our research provides valuable genetic insights that give the way for further investigation and advances in the understanding and management of hereditary cancer syndromes. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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22 pages, 3142 KiB

Open AccessArticle

JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer

by Nitin Patil, Omar G. Abdelrahim, Jörg H. Leupold and Heike Allgayer

Cancers 2024, 16(1), 24; https://doi.org/10.3390/cancers16010024 - 20 Dec 2023

Viewed by 918

Abstract

MiR-494-5p expression has been suggested to be associated with colorectal cancer (CRC) and its metastases in our previous studies. However, functional investigations on the molecule-mediating actions of this miR in CRC are lacking. In silico analysis in the present study revealed a putative binding sequence within the 3′UTR of JAK1. Overexpression of miR-494-5p in cultured CRC significantly reduced the luciferase activity of a reporter plasmid containing the wild-type JAK1-3′UTR, which was abolished by seed sequence mutation. Furthermore, the overexpression of miR-494-5p in CRC cell lines led to a significant reduction in JAK1 expression, proliferation, in vitro migration, and invasion. These effects were abolished by co-transfection with a specific double-stranded RNA that inhibits endogenous miR-494-5p. Moreover, IL-4-induced migration, invasion, and phosphorylation of JAK1, STAT6, and AKT proteins were reduced after an overexpression of this miR, suggesting that this miR affects one of the most essential pathways in CRC. A Kaplan–Meier plotter analysis revealed that patients with high JAK1 expression show reduced survival. Together, these data suggest that miR-494-5p physically inhibits the expression of JAK1 at the translational level as well as in migration and invasion, supporting the hypothesis of miR-494-5p as an early tumor suppressor and inhibitor of early steps of metastasis in CRC. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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21 pages, 4966 KiB

Open AccessArticle

Epigenetically Downregulated Breast Cancer Gene 2 through Acetyltransferase Lysine Acetyltransferase 2B Increases the Sensitivity of Colorectal Cancer to Olaparib

by Siche Chen and Heike Allgayer

Cancers 2023, 15(23), 5580; https://doi.org/10.3390/cancers15235580 - 25 Nov 2023

Viewed by 1057

Abstract

Olaparib suppresses DNA damage repair by inhibiting the poly ADP ribose polymerase (PARP), especially in cancers with BRCA1/2 mutations or the BRCA-ness phenotype. However, the first trials showed that some patients with defective DNA damage repair are still resistant to olaparib. The recovery of the wildtype BRCA is a prominent mechanism of PARP inhibitor (PARPi) resistance in BRCA-deficient tumors, but additional molecular features of olaparib resistance remain poorly understood. The objective of our study was to find molecular parameters that contribute to olaparib response or resistance in CRC. We report that histone acetyltransferase KAT2B decreases BRCA2 expression by reducing the acetylation of the 27th amino acid in histone H3 (H3K27) at the promoter of the BRCA2 gene in colorectal cancer (CRC). This increases the sensitivity of CRC cells toward olaparib treatment. The H3K27ac binding domain of BRCA2 may be required for its transcription. Low endogenous KAT2B expression, which we identify in a subset of cultured BRCA2-expressing CRC cells, leads to an accumulation of γH2AX (more DNA damage), resulting in low PARPi resistance in BRCA-expressing cells. Our results reveal KAT2B and histone acetylation as regulators of BRCA2 expression and PARPi responses in BRCA2-expressing CRC cells, providing further insights into molecular prerequisites for targeting BRCA-functional tumors. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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22 pages, 3145 KiB

Open AccessArticle

Assessment of Colorectal Cancer Risk Factors through the Application of Network-Based Approaches in a Racially Diverse Cohort of Colon Organoid Stem Cells

by Matthew Devall, Stephen Eaton, Cynthia Yoshida, Steven M. Powell, Graham Casey and Li Li

Cancers 2023, 15(14), 3550; https://doi.org/10.3390/cancers15143550 - 9 Jul 2023

Cited by 1 | Viewed by 1341

Abstract

Numerous demographic factors have been associated with colorectal cancer (CRC) risk. To better define biological mechanisms underlying these associations, we performed RNA sequencing of stem-cell-enriched organoids derived from the healthy colons of seven European Americans and eight African Americans. A weighted gene co-expression network analysis was performed following RNA sequencing. Module–trait relationships were determined through the association testing of each module and five CRC risk factors (age, body mass index, sex, smoking history, and race). Only modules that displayed a significantly positive correlation for gene significance and module membership were considered for further investigation. In total, 16 modules were associated with known CRC risk factors (p < 0.05). To contextualize the role of risk modules in CRC, publicly available RNA-sequencing data from TCGA-COAD were downloaded and re-analyzed. Differentially expressed genes identified between tumors and matched normal-adjacent tissue were overlaid across each module. Loci derived from CRC genome-wide association studies were additionally overlaid across modules to identify robust putative targets of risk. Among them, MYBL2 and RXRA represented strong plausible drivers through which cigarette smoking and BMI potentially modulated CRC risk, respectively. In summary, our findings highlight the potential of the colon organoid system in identifying novel CRC risk mechanisms in an ancestrally diverse and cellularly relevant population. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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15 pages, 1278 KiB

Open AccessArticle

Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium

by Jennifer Ose, Biljana Gigic, Stefanie Brezina, Tengda Lin, Anita R. Peoples, Pauline P. Schobert, Andreas Baierl, Eline van Roekel, Nivonirina Robinot, Audrey Gicquiau, David Achaintre, Augustin Scalbert, Fränzel J. B. van Duijnhoven, Andreana N. Holowatyj, Tanja Gumpenberger, Petra Schrotz-King, Alexis B. Ulrich, Arve Ulvik, Per-Magne Ueland, Matty P. Weijenberg, Nina Habermann, Pekka Keski-Rahkonen, Andrea Gsur, Dieuwertje E. Kok and Cornelia M. Ulrich Show full author list Hide full author list

Cancers 2023, 15(13), 3391; https://doi.org/10.3390/cancers15133391 - 28 Jun 2023

Viewed by 1974

Abstract

Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, p_FDR = 0.03; but not colon cancer: p_FDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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8 pages, 3066 KiB

Open AccessCommunication

Preclinical Evaluation of a Microwave-Based Accessory Device for Colonoscopy in an In Vivo Porcine Model with Colorectal Polyps

by Alejandra Garrido, Marta Guardiola, Luz María Neira, Roberto Sont, Henry Córdova, Miriam Cuatrecasas, Krzysztof Flisikowski, Joel Troya, Josep Sanahuja, Thomas Winogrodzki, Ignasi Belda, Alexander Meining and Glòria Fernández-Esparrach

Cancers 2023, 15(12), 3122; https://doi.org/10.3390/cancers15123122 - 8 Jun 2023

Viewed by 1230

Abstract

Background and Aims: Colonoscopy is currently the most effective way of detecting colorectal cancer and removing polyps, but it has some drawbacks and can miss up to 22% of polyps. Microwave imaging has the potential to provide a 360° view of the colon and addresses some of the limitations of conventional colonoscopy. This study evaluates the feasibility of a microwave-based colonoscopy in an in vivo porcine model. Methods: A prototype device with microwave antennas attached to a conventional endoscope was tested on four healthy pigs and three gene-targeted pigs with mutations in the adenomatous polyposis coli gene. The first four animals were used to evaluate safety and maneuverability and compatibility with endoscopic tools. The ability to detect polyps was tested in a series of three gene-targeted pigs. Results: the microwave-based device did not affect endoscopic vision or cause any adverse events such as deep mural injuries. The microwave system was stable during the procedures, and the detection algorithm showed a maximum detection signal for adenomas compared with healthy mucosa. Conclusions: Microwave-based colonoscopy is feasible and safe in a preclinical model, and it has the potential to improve polyp detection. Further investigations are required to assess the device’s efficacy in humans. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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9 pages, 1260 KiB

Open AccessReview

Endoscopic Treatment of T1 Colorectal Cancer

by Klaus Metter, Stephanie Ellen Weißinger, Alinda Várnai-Händel, Karl-Ernst Grund and Franz Ludwig Dumoulin

Cancers 2023, 15(15), 3875; https://doi.org/10.3390/cancers15153875 - 30 Jul 2023

Viewed by 1549

Abstract

Commonly accepted criteria for curative resection of T1 colorectal cancer include R0 resection with horizontal and vertical clear margins (R0), absence of lympho-vascular or vessel infiltration (L0, V0), a low to moderate histological grading (G1/2), low tumor cell budding, and limited (<1000 µm) infiltration into the submucosa. However, submucosal infiltration depth in the absence of other high-risk features has recently been questioned as a high-risk situation for lymph-node metastasis. Consequently, endoscopic resection techniques should focus on the acquisition of qualitatively and quantitively sufficient submucosal tissue. Here, we summarize the current literature on lymph-node metastasis risk after endoscopic resection of T1 colorectal cancer. Moreover, we discuss different endoscopic resection techniques with respect to the quality of the resected specimen. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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31 pages, 6981 KiB

Open AccessReview

Principles of Molecular Utility for CMS Classification in Colorectal Cancer Management

by Leili Rejali, Romina Seifollahi Asl, Fatemeh Sanjabi, Nayeralsadat Fatemi, Hamid Asadzadeh Aghdaei, Mahsa Saeedi Niasar, Pardis Ketabi Moghadam, Ehsan Nazemalhosseini Mojarad, Enrico Mini and Stefania Nobili

Cancers 2023, 15(10), 2746; https://doi.org/10.3390/cancers15102746 - 13 May 2023

Cited by 1 | Viewed by 5219

Abstract

Colorectal cancer (CRC) is the second cause of cancer-related deaths in both sexes globally and presents different clinical outcomes that are described by a range of genomic and epigenomic alterations. Despite the advancements in CRC screening plans and treatment strategies, the prognosis of CRC is dismal. In the last two decades, molecular biomarkers predictive of prognosis have been identified in CRC, although biomarkers predictive of treatment response are only available for specific biological drugs used in stage IV CRC. Translational clinical trials mainly based on “omic” strategies allowed a better understanding of the biological heterogeneity of CRCs. These studies were able to classify CRCs into subtypes mainly related to prognosis, recurrence risk, and, to some extent, also to treatment response. Accordingly, the comprehensive molecular characterizations of CRCs, including The Cancer Genome Atlas (TCGA) and consensus molecular subtype (CMS) classifications, were presented to improve the comprehension of the genomic and epigenomic landscapes of CRCs for a better patient management. The CMS classification obtained by the CRC subtyping consortium categorizes CRC into four consensus molecular subtypes (CMS1–4) characterized by different prognoses. In this review, we discussed the CMS classification in different settings with a focus on its relationships with precursor lesions, tumor immunophenotype, and gut microbiota, as well as on its role in predicting prognosis and/or response to pharmacological treatments, as a crucial step towards precision medicine. Full article

(This article belongs to the Special Issue Colorectal Cancers: From Present Problems to Future Solutions Volume II)

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