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Medicina
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Therapeutic Landscapes in Colorectal Carcinoma
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Therapeutic Landscapes in Colorectal Carcinoma

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 26121

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Antonio M Scanu

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Guest Editor
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy
Interests: genetic and epigenetic aberrations in colorectal carcinoma; MAP infection in IBD and IBS in humans; ultrasonography in Crohn’s disease stadiation; microbiota manipulation in IBD
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Maria Rosaria De Miglio

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Guest Editor
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella 4, 07100 Sassari, Italy
Interests: cancer transcriptome; cancer genetics and epigenetics; cancer metabolism; colorectal carcinoma; “triple negative” breast cancer; clear cell renal carcinoma; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Colorectal cancer (CRC) is the most frequent cancer and the third most common cause of cancer-related mortality worldwide. A high number of patients with CRC have metastases already at diagnosis, and metastatic CRC is mainly an incurable disease.

CRC is considered a heterogeneous multifactorial disease showing drastically different prognosis and response to treatment, indicating the relevance to understanding specific pathways abnormalities to improve diagnosis, prognosis, and therapeutic strategies. The opportunity to identify specific biomarkers and to detect unambiguous molecular targets, associated with early signs of cancer, will be instrumental to developing new targeted therapies and to reducing mortality for CRC. Although different critical genes and pathways have been related to the pathogenesis of CRC, for many of these genomic alterations, the prognostic and predictive roles are not known and do not influence treatment decision in metastatic conditions. Recently, the identification of K-RAS and more recently of NRAS gene mutations is a widely accepted molecular test in the clinical treatment decisions for mCRC. BRAF V600E mutation has been approved as a prognostic biomarker for identifying a cohort of patients who will have a more aggressive clinical outcome. Moreover, a relationship between MSI-high and an impressive response to immune checkpoint blockade with anti-PD1 therapy in mCRC patients has been established.

Consequently, a better understanding of the available data and a further investigation of the molecular mechanisms responsible for CRC pathogenesis are vital in order to improve CRC prevention, clinical outcome, and therapy.

We invite you and your colleagues to submit your articles reporting on this topic. Original research articles or reviews focusing on the biochemical and molecular aspects associated with pathogenesis of the human CRC; identification of circulating/tissue biomarkers in early diagnosis and management of CRC patient; and translational to clinical research on the innovative approaches for individualized therapy are invited.

Prof. Dr. Antonio M Scanu
Prof. Dr. Maria Rosaria De Miglio
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly 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 1800 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

  • Clinical, pathological, oncologic, and surgical features
  • Landscapes in immunologic and tailored therapies
  • Prognostic and therapeutic biomarkers
  • Microbiota in pathogenesis
  • Epigenetic and genetic aberrations related to resistance to anticancer therapy
  • Role of staminal cells in biology and cancer therapy
  • New drug and pharmacological approaches in cancer therapy
  • News in pathology

Published Papers (12 papers)

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Editorial

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4 pages, 257 KiB  
Editorial
Therapeutic Landscapes in Colorectal Carcinoma
by Antonio Mario Scanu and Maria Rosaria De Miglio
Medicina 2023, 59(5), 821; https://doi.org/10.3390/medicina59050821 - 23 Apr 2023
Cited by 2 | Viewed by 1378
Abstract
Colorectal cancer (CRC) is a disease of major public health and socioeconomic concern [...] Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)

Research

Jump to: Editorial, Review, Other

12 pages, 1474 KiB  
Article
Benefit of Uracil–Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer
by Po-Huang Chen, Hong-Jie Jhou, Chi-Hsiang Chung, Yi-Ying Wu, Tzu-Chuan Huang, Cho-Hao Lee, Wu-Chien Chien and Jia-Hong Chen
Medicina 2023, 59(1), 10; https://doi.org/10.3390/medicina59010010 - 20 Dec 2022
Cited by 2 | Viewed by 1620
Abstract
Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted [...] Read more.
Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489–1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542–1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352–0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475–1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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14 pages, 1856 KiB  
Article
A Reduction of Calcineurin Inhibitors May Improve Survival in Patients with De Novo Colorectal Cancer after Liver Transplantation
by Ramin Raul Ossami Saidy, Elisa Wegener, Deniz Uluk, Luca Dittrich, Wenzel Schöning, Georg Lurje, Robert Öllinger, Dominik Paul Modest, Frank Tacke, Oliver Haase, Johann Pratschke and Dennis Eurich
Medicina 2022, 58(12), 1755; https://doi.org/10.3390/medicina58121755 - 29 Nov 2022
Cited by 2 | Viewed by 1218
Abstract
Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is increased in LT patients. We assessed course of disease in patients with de novo CRC after [...] Read more.
Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is increased in LT patients. We assessed course of disease in patients with de novo CRC after LT with focus of IS and impact on survival in a retrospective, single-center study. Materials and Methods: All patients diagnosed with CRC after LT between 1988 and 2019 were included. The management of IS regimen following diagnosis and the oncological treatment approach were analyzed: Kaplan–Meier analysis as well as univariate and multivariate analysis were performed. Results: A total of 33 out of 2744 patients were diagnosed with CRC after LT. Two groups were identified: patients with restrictive IS management undergoing dose reduction (RIM group, n = 20) and those with unaltered regimen (maintenance group, n = 13). The groups did not differ in clinical and oncological characteristics. Statistically significant improved survival was found in Kaplan–Meier analysis for patients in the RIM group with 83.46 (8.4–193.1) months in RIM and 24.8 (0.5–298.9) months in the maintenance group (log rank = 0.02) and showed a trend in multivariate cox regression (p = 0.054, HR = 14.3, CI = 0.96–213.67). Conclusions: Immunosuppressive therapy should be reduced further in patients suffering from CRC after LT in an individualized manner to enable optimal oncological therapy and enable improved survival. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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13 pages, 916 KiB  
Article
Efficacy and Safety of Neoadjuvant Chemotherapy Combined with Adjuvant Chemotherapy for Locally Advanced Colon Cancer: A Propensity Score-Matching Analysis
by Wei Zeng, Yi Liu, Chuandong Wang, Changshun Yang, Shengtao Lin and Weihua Li
Medicina 2022, 58(11), 1505; https://doi.org/10.3390/medicina58111505 - 22 Oct 2022
Cited by 5 | Viewed by 1555
Abstract
Background and Objectives: Increasing evidence supports the use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC). However, its effectiveness remains controversial. This study explored the safety and efficacy of NAC combined with laparoscopic radical colorectal cancer surgery and adjuvant chemotherapy [...] Read more.
Background and Objectives: Increasing evidence supports the use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC). However, its effectiveness remains controversial. This study explored the safety and efficacy of NAC combined with laparoscopic radical colorectal cancer surgery and adjuvant chemotherapy (AC) for LACC. Materials and Methods: We retrospectively analyzed 444 patients diagnosed with LACC (cT4 or cT3, with ≥5 mm invasion beyond the muscularis propria) in our hospital between 2012 and 2015. Propensity score matching (PSM; 1:2) was performed to compare patients treated with NAC and those treated with adjuvant chemotherapy (AC). Results: Overall, 42 patients treated with NAC were compared with 402 patients who received only AC. After PSM, 42 patients in the NAC group were compared with 84 patients in the control group, with no significant differences in the baseline characteristics between groups. The pathological tumor sizes in the NAC group were significantly smaller than those in the AC group (3.1 ± 2.1 cm vs. 5.8 ± 2.5 cm). Patients in the NAC group had a significantly lower T stage than those in the AC group (p < 0.001). After neoadjuvant chemotherapy, a significant response was observed in four (9.6%) patients, with two (4.8%) showing a complete response. The 5-year overall survival rates (88.1% vs. 77.8%, p = 0.206) and 5-year disease-free survival rates (75.1% vs. 64.2%, p = 0.111) did not differ between the groups. However, the 5-year cumulative rate of distant recurrence was significantly lower in the NAC than in the AC group (9.6% vs. 29.9%, p = 0.022). Conclusions: NAC, combined with AC, could downstage primary tumors of LACC and seems safe and acceptable for patients with LACC, with a similar long-term survival between the two treatments. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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15 pages, 563 KiB  
Article
Sensitivities and Dependencies of BRAF Mutant Colorectal Cancer Cell Lines with or without PIK3CA Mutations for Discovery of Vulnerabilities with Therapeutic Potential
by Ioannis A. Voutsadakis
Medicina 2022, 58(10), 1498; https://doi.org/10.3390/medicina58101498 - 21 Oct 2022
Cited by 3 | Viewed by 1935
Abstract
Background: Colorectal cancer represents a common malignancy and remains incurable in the metastatic stage. Identification of molecular alterations that are present in colorectal cancer has led to the introduction of targeted therapies that improve outcomes. BRAF and PIK3CA mutations are observed in a [...] Read more.
Background: Colorectal cancer represents a common malignancy and remains incurable in the metastatic stage. Identification of molecular alterations that are present in colorectal cancer has led to the introduction of targeted therapies that improve outcomes. BRAF and PIK3CA mutations are observed in a subset of colorectal cancers. Colorectal cancers bearing BRAF mutations may be treated with specific BRAF inhibitors. These drugs benefit patients with BRAF mutant colorectal cancers but responses are rather brief, and progression is the rule. In contrast, no PI3K inhibitors have proven successful yet in the disease. Thus, new treatments to supplement the currently available drugs would be welcome to further improve survival. Methods: Profiled colorectal cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE) were examined for BRAF and PIK3CA mutations and were interrogated for molecular characteristics and concomitant alterations that mirror clinical sample alterations. The Genomics of Drug Sensitivity in Cancer (GDSC) project was used for determination of drug sensitivities of BRAF mutated colorectal cell lines with or without concomitant PIK3CA mutations. The Cancer Dependency Map project served as the basis for identification of molecular dependencies and vulnerabilities in these cell lines. Results: CCLE includes 84 colorectal cancer cell lines, which recapitulate the molecular landscape of colorectal cancer. Of these, 23 and 24 cell lines possess BRAF and PIK3CA mutations, respectively. Seven BRAF mutant cell lines have V600E mutations and 14 PIK3CA mutant cell lines have hotspot helical or kinase domain mutations. V600E BRAF mutant cell lines with or without hotspot PIK3CA mutations are heterogeneous in their MSI status and mimic colorectal cancer tissues in other prevalent abnormalities including APC and TP53 mutations. Essential genes for survival include CTNNB1, WRN, and pyrimidine metabolism enzyme CAD. Besides BRAF mutations, BRAF inhibitor sensitivity in colorectal cancer cell lines is conferred by SACS mutations and PRKN locus loss. Conclusions: Colorectal cancer cell lines bearing the frequent BRAF and PIK3CA mutations present many alterations of the parental cancer tissue. Described vulnerabilities represent leads for therapeutic exploration in colorectal cancers with the corresponding alterations. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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10 pages, 790 KiB  
Article
BRAF, MEK, and EGFR Triplet Inhibitors as Salvage Therapy in BRAF-Mutated Metastatic Colorectal Cancer—A Case Series Study Target Therapy of BRAF-Mutated mCRC
by Jen-Hao Yeh, Hsiang-Lin Tsai, Yen-Cheng Chen, Ching-Chun Li, Ching-Wen Huang, Tsung-Kun Chang, Wei-Chih Su, Po-Jung Chen, Yu-Peng Liu and Jaw-Yuan Wang
Medicina 2021, 57(12), 1339; https://doi.org/10.3390/medicina57121339 - 07 Dec 2021
Cited by 7 | Viewed by 2114
Abstract
Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. [...] Read more.
Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1–26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1–2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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12 pages, 324 KiB  
Article
Cell Models for Chromosome 20q11.21 Amplification and Drug Sensitivities in Colorectal Cancer
by Ioannis A. Voutsadakis
Medicina 2021, 57(9), 860; https://doi.org/10.3390/medicina57090860 - 24 Aug 2021
Cited by 2 | Viewed by 1995
Abstract
Background and objectives: The chromosome locus 20q11.21 is a commonly amplified locus in colorectal cancer, with a prevalence of 8% to 9%. Several candidate cancer-associated genes are transcribed from the locus. The therapeutic implications of the amplification in colorectal cancer remain unclear. [...] Read more.
Background and objectives: The chromosome locus 20q11.21 is a commonly amplified locus in colorectal cancer, with a prevalence of 8% to 9%. Several candidate cancer-associated genes are transcribed from the locus. The therapeutic implications of the amplification in colorectal cancer remain unclear. Materials and Methods: Preclinical cell line models of colorectal cancer included in the Cancer Cell Line Encyclopedia (CCLE) collection were examined for the presence of amplifications in 20q11.21 genes. Correlations of the presence of 20q11.21 amplifications with gene essentialities and drug sensitivities were surveyed on salient databases for determination of therapeutic leads. Results: A significant subset of colorectal cancer cell lines in the CCLE (12 of 63 cell lines, 19%) bear amplifications of genes located at 20q11.21. Cancer-associated genes of the locus include ASXL1, DNMT3B, BCL2L1, TPX2, KIF3B and POFUT1. These genes are all amplified in the 12 cell lines, but they are variably over-expressed at the mRNA level, compared to non-amplified lines. 20q11.21 amplified cell lines are sensitive to various tyrosine kinase inhibitors and are resistant to chemotherapy drugs targeting the mitotic apparatus and microtubules. CRISPR and RNAi dependencies screening revealed, besides the β-catenin and KRAS genes, a few recurrent gene dependencies in more than one cell line, including YAP1 and JUP. Conclusions: Cell line models of colorectal cancer with 20q11.21 gene amplifications display dependencies on the presence of specific genes and resistance or sensitivity to specific drugs and drug categories. Observations from in vitro models may form the basis for clinical drug development in this subtype of colorectal cancer. Genetic lesions conferring synthetic lethality to certain drugs or categories of drugs could be discovered with this approach. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
8 pages, 965 KiB  
Article
An Insight into Deficient Mismatch Repair Colorectal Cancer Screening in a Romanian Population—A Bi-Institutional Pilot Study
by Cristina Lungulescu, Vlad Mihai Croitoru, Simona Ruxandra Volovat, Irina Mihaela Cazacu, Adina Turcu-Stiolica, Dan Ionut Gheonea, Daniel Sur and Cristian Virgil Lungulescu
Medicina 2021, 57(8), 847; https://doi.org/10.3390/medicina57080847 - 20 Aug 2021
Cited by 3 | Viewed by 2669
Abstract
Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation [...] Read more.
Background and Objectives: Colorectal cancer (CRC) can be classified as mismatch-repair-deficient (dMMR) with high levels of microsatellite instability (MSI-H), or mismatch-repair-proficient (pMMR) and microsatellite stable (MSS). Approximately 15% of patients have microsatellite instability (MSI). MSI-H tumors are associated with a high mutation burden. Monoclonal antibodies that block immune checkpoints can induce long-term durable responses in some patients. Pembrolizumab is the first checkpoint inhibitor approved in the EU to treat dMMR–MSI-H metastatic CRC. Materials and Methods: Our study assesses the regional variability of MSI-H colorectal cancer tumors in Romania. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks containing tumor samples from 90 patients diagnosed with colorectal cancer were collected from two tertiary referral Oncology Centers from Romania. Tissues were examined for the expression loss of MMR proteins (MLH1, PMS2, MSH2, MSH6) using immunohistochemistry or MSI status using polymerase chain reaction (PCR), respectively. Results: MSI-H was detected in 19 (21.1%) patients. MSI-H was located more in ascending colon (36.8% vs. 9.9%, p-value = 0.0039) and less in sigmoid (5.3% vs. 33.8%, p-value = 0.0136) than MSS patients. Most patients were stage II for MSI-H (42.1%) as well as for MSS (56.3%), with significant more G1 (40.9% vs. 15.8%, p-value = 0.0427) for MSS patients. Gender, N stage, and M stage were identified as significant prognostic factors in multivariate analysis. MSI status was not a statistically significant predictor neither in univariate analysis nor multivariate analysis. Conclusion: Considering the efficacy of PD-1 inhibitor in metastatic CRC with MSI-H or dMMR, and its recent approval in EU, it is increasingly important to understand the prevalence across tumor stage, histology, and demographics, since our study displayed higher regional MSI-H prevalence (21%) compared to the literature. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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9 pages, 706 KiB  
Article
Receptor-Interacting Serine/Threonine-Protein Kinase-2 as a Potential Prognostic Factor in Colorectal Cancer
by Rola F. Jaafar, Zeid Ibrahim, Karim Ataya, Joelle Hassanieh, Natasha Ard and Walid Faraj
Medicina 2021, 57(7), 709; https://doi.org/10.3390/medicina57070709 - 14 Jul 2021
Cited by 10 | Viewed by 2662
Abstract
Background and objectives: Receptor-interacting serine/threonine-protein kinase-2 (RIPK2) is an important mediator in different pathways in the immune and inflammatory response system. RIPK2 was also shown to play different roles in different cancer types; however, in colorectal cancer (CRC), its role is not [...] Read more.
Background and objectives: Receptor-interacting serine/threonine-protein kinase-2 (RIPK2) is an important mediator in different pathways in the immune and inflammatory response system. RIPK2 was also shown to play different roles in different cancer types; however, in colorectal cancer (CRC), its role is not well established. This study aims at identifying the role of RIPK2 in CRC progression and survival. Materials and methods: Data of patients and mRNA protein expression level of genes associated with CRC (RIPK2, tumor necrosis factor (TNF), TRAF1, TRAF7, KLF6, interlukin-6 (Il6), interlukin-8 (Il8), vascular-endothelial growth factor A (VEGFA), MKI67, TP53, nuclear factor-kappa B (NFKB), NFKB2, BCL2, XIAP, and RELA) were downloaded from the PrognoScan online public database. Patients were divided between low and high RIPK2 expression and different CRC characteristics were studied between the two groups. Survival curves were evaluated using a Kaplan–Meier estimator. The Pearson correlation was used to study the correlation between RIPK2 and the other factors. Statistical analysis was carried out using SPSS version 25.0. The Human Protein Atlas was also used for the relationship between RIPK2 expression in CRC tissues and survival. Differences were considered statistically significant at p < 0.05. Results: A total of 520 patients were downloaded from the PrognoScan database, and RIPK2 was found to correlate with MKI67, TRAF1, KLF6, TNF, Il6, Il8, VEGFA, NFKB2, BCL2, and RELA. High expression of RIPK2 was associated with high expression of VEGFA (p < 0.01) and increased mortality (p < 0.01). Conclusions: In this study, RIPK2 is shown to be a potential prognostic factor in CRC; however, more studies are needed to assess and verify its potential role as a prognostic marker and in targeted therapy. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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Review

Jump to: Editorial, Research, Other

9 pages, 426 KiB  
Review
Global Impact of COVID-19 on Colorectal Cancer Screening: Current Insights and Future Directions
by Jonathan Kopel, Bojana Ristic, Gregory L. Brower and Hemant Goyal
Medicina 2022, 58(1), 100; https://doi.org/10.3390/medicina58010100 - 10 Jan 2022
Cited by 11 | Viewed by 2894
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has brought significant challenges to many aspects of healthcare delivery since the first reported case in early December 2019. Once in the body, SARS-CoV-2 can spread to other digestive organs, such as the liver, because of the [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has brought significant challenges to many aspects of healthcare delivery since the first reported case in early December 2019. Once in the body, SARS-CoV-2 can spread to other digestive organs, such as the liver, because of the presence of ACE2 receptors. Colorectal cancer (CRC) remains the second-leading cause of death in the United States (US). Therefore, individuals are routinely screened using either endoscopic methods (i.e., flexible sigmoidoscopy and colonoscopy) or stool-based tests, as per the published guidelines. At the beginning of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services (CMS) recommended that all non-urgent surgical and medical procedures, including screening colonoscopies, be delayed until the pandemic stabilization. This article aims to review the impact of COVID-19 on CRC screening. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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16 pages, 505 KiB  
Review
A Portrait of Intratumoral Genomic and Transcriptomic Heterogeneity at Single-Cell Level in Colorectal Cancer
by Andrea Angius, Antonio Mario Scanu, Caterina Arru, Maria Rosaria Muroni, Ciriaco Carru, Alberto Porcu, Paolo Cossu-Rocca and Maria Rosaria De Miglio
Medicina 2021, 57(11), 1257; https://doi.org/10.3390/medicina57111257 - 17 Nov 2021
Cited by 5 | Viewed by 2888
Abstract
In the study of cancer, omics technologies are supporting the transition from traditional clinical approaches to precision medicine. Intra-tumoral heterogeneity (ITH) is detectable within a single tumor in which cancer cell subpopulations with different genome features coexist in a patient in different tumor [...] Read more.
In the study of cancer, omics technologies are supporting the transition from traditional clinical approaches to precision medicine. Intra-tumoral heterogeneity (ITH) is detectable within a single tumor in which cancer cell subpopulations with different genome features coexist in a patient in different tumor areas or may evolve/differ over time. Colorectal carcinoma (CRC) is characterized by heterogeneous features involving genomic, epigenomic, and transcriptomic alterations. The study of ITH is a promising new frontier to lay the foundation towards successful CRC diagnosis and treatment. Genome and transcriptome sequencing together with editing technologies are revolutionizing biomedical research, representing the most promising tools for overcoming unmet clinical and research challenges. Rapid advances in both bulk and single-cell next-generation sequencing (NGS) are identifying primary and metastatic intratumoral genomic and transcriptional heterogeneity. They provide critical insight in the origin and spatiotemporal evolution of genomic clones responsible for early and late therapeutic resistance and relapse. Single-cell technologies can be used to define subpopulations within a known cell type by searching for differential gene expression within the cell population of interest and/or effectively isolating signal from rare cell populations that would not be detectable by other methods. Each single-cell sequencing analysis is driven by clustering of cells based on their differentially expressed genes. Genes that drive clustering can be used as unique markers for a specific cell population. In this review we analyzed, starting from published data, the possible achievement of a transition from clinical CRC research to precision medicine with an emphasis on new single-cell based techniques; at the same time, we focused on all approaches and issues related to this promising technology. This transition might enable noninvasive screening for early diagnosis, individualized prediction of therapeutic response, and discovery of additional novel drug targets. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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Other

9 pages, 2086 KiB  
Case Report
A Promising Role of TGF-β Pathway in Response to Regorafenib in Metastatic Colorectal Cancer: A Case Report
by Simona De Summa, Katia Danza, Brunella Pilato, Giuseppina Matera, Rossella Fasano, Angela Calabrese, Rosanna Lacalamita, Nicola Silvestris, Stefania Tommasi, Antonella Argentiero and Oronzo Brunetti
Medicina 2021, 57(11), 1241; https://doi.org/10.3390/medicina57111241 - 13 Nov 2021
Cited by 3 | Viewed by 1690
Abstract
Colorectal cancer (CRC) is one of the most common cancer types around the world. The prognosis of patients with advanced diseases is still poor in spite of currently available therapeutic options. Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved to treat refractory [...] Read more.
Colorectal cancer (CRC) is one of the most common cancer types around the world. The prognosis of patients with advanced diseases is still poor in spite of currently available therapeutic options. Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved to treat refractory metastatic colorectal cancer (mCRC). We investigated Somatic mutations in several genes involved in immunological response and cancer progression in both long/short responder mCRC patients who underwent third-line therapy with regorafenib to identify predictive biomarkers of response using Ion Torrent PGM sequencing and bioinformatic tools. We found Somatic mutations in TGFBR1, TGFBR2, and TGFBR3 genes in primary tumor and metastases samples of long-responder patients. Furthermore, our bioinformatic results show that they were mainly enriched in immune response, cell junction, and cell adhesion in long responder patients, particularly in primary tumor and metastatic sites. These data suggest that the TGF-b pattern could be the leading actor of a prolonged response to this drug. Full article
(This article belongs to the Special Issue Therapeutic Landscapes in Colorectal Carcinoma)
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