Topic Editors

Dr. Niki Christou
1 UMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, France 2 Department of General, Endocrine and Digestive Surgery, University Hospital of Limoges, 87025 Limoges, France
UMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, France
Dr. Fabrice Lalloué
UMR INSERM 1308-CAPTuR “Control of Cell Activation in Tumor Progression and Therapeutic Resistance”, Ω-Health Institute, Faculty of Medicine, University of Limoges, 87025 Limoges, France

Advances in Colorectal Cancer Therapy

Abstract submission deadline
20 October 2024
Manuscript submission deadline
20 December 2024
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Topic Information

Dear Colleagues,

Colorectal cancer is the 3rd most common cancer worldwide, with a mean age of diagnosis at around 71 years old. Recent data suggest an increased incidence of cases in young people. Moreover, despite improvements in prognosis thanks to targeted therapies over the past two decades, the rate of recurrence or resistance to treatment remains high. For instance, for stage 3, this rate reaches 30%, despite well-conducted curative treatment. Its complexity is in part related to the heterogeneity present within the tumor. Therefore, this Special Issue will consider articles on all types of research, from fundamental to translational and clinical, to shed light on the evolution of therapies in colon and rectal cancers and all the new diagnostic, prognostic, and theragnostic strategies that international research teams are currently developing.

Dr. Niki Christou
Dr. Mireille Verdier
Dr. Fabrice Lalloué
Topic Editors

Keywords

  • colon cancer
  • rectal cancer
  • biology mechanisms
  • prognostic markers
  • therapies
  • clinical management

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
Biomedicines
biomedicines
4.7 3.7 2013 15.4 Days CHF 2600 Submit
Cancers
cancers
5.2 7.4 2009 17.9 Days CHF 2900 Submit
Cells
cells
6.0 9.0 2012 16.6 Days CHF 2700 Submit
International Journal of Molecular Sciences
ijms
5.6 7.8 2000 16.3 Days CHF 2900 Submit
Onco
onco
- - 2021 18.3 Days CHF 1000 Submit

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Published Papers (14 papers)

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15 pages, 947 KiB  
Article
First-Line LV5FU2 with or without Aflibercept in Patients with Non-Resectable Metastatic Colorectal Cancer: A Randomized Phase II Trial (PRODIGE 25-FFCD-FOLFA)
by Jean-Louis Legoux, Roger Faroux, Nicolas Barrière, Karine Le Malicot, David Tougeron, Véronique Lorgis, Véronique Guerin-Meyer, Vincent Bourgeois, David Malka, Thomas Aparicio, Matthieu Baconnier, Valérie Lebrun-Ly, Joëlle Egreteau, Faïza Khemissa Akouz, Magali Terme, Côme Lepage and Valérie Boige
Cancers 2024, 16(8), 1515; https://doi.org/10.3390/cancers16081515 - 16 Apr 2024
Viewed by 282
Abstract
Fluropyrimidine monotherapy is an option for some patients with inoperable metastatic colorectal cancer. Unlike bevacizumab, the addition of aflibercept, an antibody acting as an anti-angiogenic agent, has never been evaluated in this context. The aim of the study was to determine whether aflibercept [...] Read more.
Fluropyrimidine monotherapy is an option for some patients with inoperable metastatic colorectal cancer. Unlike bevacizumab, the addition of aflibercept, an antibody acting as an anti-angiogenic agent, has never been evaluated in this context. The aim of the study was to determine whether aflibercept could increase the efficacy of fluoropyrimidine monotherapy without increasing toxicity. This multicenter phase II non-comparative trial evaluated the addition of aflibercept to infusional 5-fluorouracil/folinic acid (LV5FU2 regimen) as first-line treatment in patients unfit to receive doublet cytotoxic chemotherapy. The primary endpoint was 6-month progression-free survival (PFS). The clinical hypotheses expected a PFS rate at 6 months of over 40% (60% expected). A total of 117 patients, with a median age of 81 years, were included: 59 in arm A (LV5FU2-aflibercept) and 58 in arm B (LV5FU2 alone). Six-month PFS was 54.7% in both arms (90% CI 42.5–66.5 in both). Median overall survival was 21.8 months (arm A) and 25.1 months (arm B). Overall toxicity was more common in arm A: grade ≥ 3 toxicity in 82% versus 58.2%. Given the 6-month PFS, the study can be considered positive. However, the toxicity of aflibercept in this population was high, and continuation of the trial into phase III is not envisaged. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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3 pages, 133 KiB  
Editorial
Sunglasses for Sunlight: Considerations on New Treatment Opportunities for Refractory Colorectal Cancer
by Alberto Zaniboni
Cancers 2024, 16(7), 1348; https://doi.org/10.3390/cancers16071348 - 29 Mar 2024
Viewed by 367
Abstract
In 2023, two seminal studies were disseminated that significantly augmented the pharmacological armamentarium for the treatment of refractory metastatic colorectal carcinoma (MCRC) [...] Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
18 pages, 2718 KiB  
Article
EGFR-Targeted Antibody–Drug Conjugate to Different Aminobisphosphonates: Direct and Indirect Antitumor Effects on Colorectal Carcinoma Cells
by Leila Pisheh, Serena Matis, Martina Taglieri, Linda Di Gregorio, Roberto Benelli and Alessandro Poggi
Cancers 2024, 16(7), 1256; https://doi.org/10.3390/cancers16071256 - 22 Mar 2024
Viewed by 609
Abstract
Antibody––drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a “biological missile” that can destroy tumor [...] Read more.
Antibody––drug conjugates (ADCs) are a promising delivery system that involves linking a monoclonal antibody (mAb) to a specific drug, such as a cytotoxic agent, to target tumor cells. This new class of antitumor therapy acts as a “biological missile” that can destroy tumor cells while increasing the therapeutic index and decreasing toxicity. One of the most critical factors in ADC design is selecting a target antigen that is highly expressed on the surface of cancer cells. In this study, we conjugated Cetuximab (Cet), a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to aminobisphosphonates (N-BPs) such as ibandronate (IBA) or risedronate (RIS) or zoledronate (ZA). Cetuximab is administered to patients with metastatic colorectal carcinoma (mCRC) with a wild-type (WT) EGFR transduction pathway. Also, it is well established that N-BPs can trigger the antitumor activity of Vδ2 T cells in both in vitro and in vivo experimental models. The resulting ADCs were added in co-culture to assess the effect on CRC cell line proliferation and sensitivity to Vδ2 T antitumor lymphocytes in comparison with the native antibody. These assays have been performed both in conventional and 3D spheroid cultures. We found that all three ADCs can increase the inhibitory effect on cell proliferation of the WT-EGFR cell line Caco-2 while only Cet-RIS and Cet-ZA can increase the cytotoxicity mediated by Vδ2 T cells against both WT and EGFR-mutated CRC cell lines (Caco-2, DLD-1, and HCT-116). Also, the ADCs can trigger the cell proliferation of Vδ2 T cells present in peripheral blood and tumor specimens. Our findings indicate that anti-EGFR antibodies bound to N-BPs can improve the antitumor effects of the native antibody possibly increasing the therapeutic effect. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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15 pages, 2006 KiB  
Systematic Review
Systemic Chemotherapy in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery: Systematic Review and Meta-Analysis
by Marco Tonello, Carola Cenzi, Elisa Pizzolato, Riccardo Fiscon, Paola Del Bianco, Pierluigi Pilati and Antonio Sommariva
Cancers 2024, 16(6), 1182; https://doi.org/10.3390/cancers16061182 - 18 Mar 2024
Viewed by 564
Abstract
Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on [...] Read more.
Background. For patients with colorectal cancer (CRC) peritoneal metastases (PM) who are eligible for cytoreductive surgery (CRS), the indication and timing of systemic chemotherapy (SC) are still under debate. This study aims to analyze the role of pre, post or perioperative SC on the survival and surgical complications of patients treated with CRS-HIPEC. Methods. After a systematic search in MEDLINE, Cochrane Database of Systematic Reviews, Scopus, Web of Science and Embase, a meta-analysis was performed to compare postoperative complications, disease-free survival (DFS) and overall survival (OS) according to SC administration and timing. PROSPERO: CRD42023478977. Results. Of 1203 studies screened, 15 were included in the meta-analysis (4523 patients). Post-operative SC was associated with increased overall survival (post-SC vs. no post-SC: HR 0.81, p = 0.00001, I2 = 0%; pre-SC vs. post-SC: HR 0.65, p = 0.01, I2 = 28%), whereas SC (pre or post) or pre-SC compared to surgery alone was not (SC vs. no SC: p = 0.29, I2 = 80%; pre-SC vs. no pre-SC: p = 0.59, I2 = 58%). Similar results were seen for DFS. SC was not associated with an increased complication rate (p = 0.47, I2 = 64%). Conclusions. Systemic chemotherapy administration in patients undergoing radical surgery for colorectal peritoneal metastases is associated with increased survival only in the adjuvant/post-operative setting. Considering the limitations of the included studies, further trials are needed to answer this unresolved question. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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17 pages, 6497 KiB  
Article
Hypermethylated Colorectal Cancer Tumours Present a Myc-Driven Hypermetabolism with a One-Carbon Signature Associated with Worsen Prognosis
by Christophe Desterke, Fanny Jaulin and Emmanuel Dornier
Biomedicines 2024, 12(3), 590; https://doi.org/10.3390/biomedicines12030590 - 06 Mar 2024
Viewed by 668
Abstract
Colorectal cancer (CRC) is the second cause of cancer-related death; the CpG-island methylation pathway (CIMP) is associated with KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worse prognosis, and resistance to classical chemotherapies. Despite this, the question of a possible metabolic rewiring in CIMPs [...] Read more.
Colorectal cancer (CRC) is the second cause of cancer-related death; the CpG-island methylation pathway (CIMP) is associated with KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worse prognosis, and resistance to classical chemotherapies. Despite this, the question of a possible metabolic rewiring in CIMPs has never been investigated. Here, we analyse whether metabolic dysregulations are associated with tumour methylation by evaluating the transcriptome of CRC tumours. CIMP-high patients were found to present a hypermetabolism, activating mainly carbohydrates, folates, sphingolipids, and arachidonic acid metabolic pathways. A third of these genes had epigenetic targets of Myc in their proximal promoter, activating carboxylic acid, tetrahydrofolate interconversion, nucleobase, and oxoacid metabolisms. In the Myc signature, the expression of GAPDH, TYMS, DHFR, and TK1 was enough to predict methylation levels, microsatellite instability (MSI), and mutations in the mismatch repair (MMR) machinery, which are strong indicators of responsiveness to immunotherapies. Finally, we discovered that CIMP tumours harboured an increase in genes involved in the one-carbon metabolism, a pathway critical to providing nucleotides for cancer growth and methyl donors for DNA methylation, which is associated with worse prognosis and tumour hypermethylation. Transcriptomics could hence become a tool to help clinicians stratify their patients better. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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15 pages, 4172 KiB  
Article
Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer
by Liza A. Wijler, Bastiaan J. Viergever, Esther Strating, Susanne J. van Schelven, Susanna Poghosyan, Nicola C. Frenkel, Hedy te Rietmole, Andre Verheem, Danielle A. E. Raats, Inne H. M. Borel Rinkes, Jeroen Hagendoorn and Onno Kranenburg
Cancers 2024, 16(5), 1073; https://doi.org/10.3390/cancers16051073 - 06 Mar 2024
Viewed by 771
Abstract
Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood. Here, we [...] Read more.
Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood. Here, we tested the hypothesis that the site of tumor growth influences extra-hepatic metastasis formation. To this end, we implanted murine colon cancer organoids into the primary tumor site (i.e., the caecum) and into the primary metastasis site (i.e., the liver) in immunocompetent mice. The organoid-initiated liver tumors were significantly more efficient in seeding distant metastases compared to tumors of the same origin growing in the caecum (intra-hepatic: 51 vs. 40%, p = 0.001; peritoneal cavity: 51% vs. 33%, p = 0.001; lungs: 30% vs. 7%, p = 0.017). The enhanced metastatic capacity of the liver tumors was associated with the formation of ‘hotspots’ of vitronectin-positive blood vessels surrounded by macrophages. RNA sequencing analysis of clinical samples showed a high expression of vitronectin in liver metastases, along with signatures reflecting hypoxia, angiogenesis, coagulation, and macrophages. We conclude that ‘onward spread’ from liver metastases is facilitated by liver-specific microenvironmental signals that cause the formation of macrophage-associated vascular hotspots. The therapeutic targeting of these signals may help to contain the disease within the liver and prevent onward spread. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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15 pages, 2987 KiB  
Article
Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis
by Feiyan Zhao, Keizo Hiraishi, Xiaodong Li, Yaopeng Hu, Daibo Kojima, Zhihong Sun, Heping Zhang and Lin-Hai Kurahara
Biomedicines 2024, 12(3), 531; https://doi.org/10.3390/biomedicines12030531 - 27 Feb 2024
Viewed by 792
Abstract
Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the [...] Read more.
Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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19 pages, 2966 KiB  
Article
Assessment of an Anticancer Effect of the Simultaneous Administration of MM-129 and Indoximod in the Colorectal Cancer Model
by Iwona Kwiatkowska, Justyna Magdalena Hermanowicz, Robert Czarnomysy, Arkadiusz Surażyński, Krystyna Kowalczuk, Joanna Kałafut, Alicja Przybyszewska-Podstawka, Krzysztof Bielawski, Adolfo Rivero-Müller, Mariusz Mojzych and Dariusz Pawlak
Cancers 2024, 16(1), 122; https://doi.org/10.3390/cancers16010122 - 26 Dec 2023
Viewed by 833
Abstract
(1) Background: The purpose of the given study was to examine the antitumor activity of the simultaneous administration of MM-129, a 1,2,4-triazine derivative, and indoximod (IND), the kynurenine pathway inhibitor, toward colon cancer. (2) Methods: The efficiency of the co-administration of the studied [...] Read more.
(1) Background: The purpose of the given study was to examine the antitumor activity of the simultaneous administration of MM-129, a 1,2,4-triazine derivative, and indoximod (IND), the kynurenine pathway inhibitor, toward colon cancer. (2) Methods: The efficiency of the co-administration of the studied compounds was assessed in xenografted zebrafish embryos. Then, the effects of the combined administration of compounds on cellular processes such as cell viability, apoptosis, and intracellular signaling pathways were evaluated. In vitro studies were performed using two colorectal cancer cell lines, namely, DLD-1 and HT-29. (3) Results: The results indicated that the simultaneous application of MM-129 and indoximod induced a stronger inhibition of tumor growth in zebrafish xenografts. The combination of these compounds intensified the process of apoptosis by lowering the mitochondrial potential, enhancing the externalization of phosphatidylserine (PS) and activation of caspases. Additionally, the expression of protein kinase B (AKT) and indoleamine 2,3-dioxygenase-(1IDO1) was disrupted under the applied compound combination. (4) Conclusions: Simultaneous targeting of ongoing cell signaling that promotes tumor progression, along with inhibition of the kynurenine pathway enzyme IDO1, results in the enhancement of the antitumor effect of the tested compounds against the colon cancer cells. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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14 pages, 2971 KiB  
Article
Beta-Hydroxybutyrate Augments Oxaliplatin-Induced Cytotoxicity by Altering Energy Metabolism in Colorectal Cancer Organoids
by Tolga Sever, Ender Berat Ellidokuz, Yasemin Basbinar, Hulya Ellidokuz, Ömer H. Yilmaz and Gizem Calibasi-Kocal
Cancers 2023, 15(24), 5724; https://doi.org/10.3390/cancers15245724 - 06 Dec 2023
Viewed by 1881
Abstract
Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) [...] Read more.
Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) cycle, possibly redirecting energy metabolic pathways towards the TCA cycle that could enhance sensitivity to oxaliplatin, through the generation of reactive oxygen species (ROS). This study explores the potential of BOHB to enhance oxaliplatin’s cytotoxic effect by altering the energy metabolism in colorectal cancer. The study employed advanced in vitro organoid technology, which successfully emulates in vivo physiology. The combination treatment efficacy of BOHB and oxaliplatin was evaluated via cell viability assay. The levels of key proteins involved in energy metabolism, apoptotic pathways, DNA damage markers, and histone acetylation were analyzed via Western Blot. ROS levels were evaluated via flow cytometer. Non-toxic doses of BOHB with oxaliplatin significantly amplified cytotoxicity in colorectal cancer organoids. Treatment with BOHB and/or melatonin resulted in significantly decreased lactate dehydrogenase A and increased mitochondrial carrier protein 2 levels, indicating inhibited aerobic glycolysis and an increased oxidative phosphorylation rate. This metabolic shift induced apoptotic cell death mediated by oxaliplatin, owing to high levels of ROS. Melatonin counteracted this effect by protecting cancer cells from high oxidative stress conditions. BOHB may enhance the efficacy of chemotherapeutics with a similar mechanism of action to oxaliplatin in colorectal cancer treatment. These innovative combinations could improve treatment outcomes for colorectal cancer patients. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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13 pages, 1869 KiB  
Article
Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study
by Karmele Saez de Gordoa, Maria Teresa Rodrigo-Calvo, Ivan Archilla, Sandra Lopez-Prades, Alba Diaz, Jordi Tarragona, Isidro Machado, Juan Ruiz Martín, Diana Zaffalon, Maria Daca-Alvarez, Maria Pellisé, Jordi Camps and Miriam Cuatrecasas
Cancers 2023, 15(22), 5481; https://doi.org/10.3390/cancers15225481 - 20 Nov 2023
Viewed by 734
Abstract
Early-stage colorectal carcinoma (CRC)—pT1—is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5–2%. Among these cases, approximately 6–16% exhibit LNM, [...] Read more.
Early-stage colorectal carcinoma (CRC)—pT1—is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5–2%. Among these cases, approximately 6–16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/μL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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11 pages, 1169 KiB  
Article
Circulating Tumour DNA Guided Adjuvant Chemotherapy Decision Making in Stage II Colon Cancer—A Clinical Vignette Study
by Yat Hang To, Peter Gibbs, Jeanne Tie, Jonathan Loree, Tamara Glyn and Koen Degeling
Cancers 2023, 15(21), 5227; https://doi.org/10.3390/cancers15215227 - 31 Oct 2023
Viewed by 845
Abstract
Circulating tumour DNA (ctDNA) is a promising biomarker that may better identify stage II colon cancer (CC) patients who will benefit from adjuvant chemotherapy (AC) compared to standard clinicopathological parameters. The DYNAMIC study demonstrated that ctDNA-informed treatment decreased AC utilisation without compromising recurrence [...] Read more.
Circulating tumour DNA (ctDNA) is a promising biomarker that may better identify stage II colon cancer (CC) patients who will benefit from adjuvant chemotherapy (AC) compared to standard clinicopathological parameters. The DYNAMIC study demonstrated that ctDNA-informed treatment decreased AC utilisation without compromising recurrence free survival, but medical oncologists’ willingness to utilise ctDNA results to inform AC decision is unknown. Medical oncologists from Australia, Canada and New Zealand were presented with clinical vignettes for stage II CC comprised of two variables with three levels each (age: ≤50, 52–69, ≥70 years; and clinicopathological risk of recurrence: low, intermediate, high) and were queried about ctDNA testing and treatment recommendations based on results. Sixty-four colorectal oncologists completed at least one vignette (all vignettes, n = 59). The majority of oncologist were Australian (70%; Canada: n = 13; New Zealand: n = 6) and had over 10 years of clinical experience (n = 41; 64%). The proportion of oncologists requesting ctDNA testing exceeded 80% for all vignettes, except for age ≥ 70 and low-risk disease (63%). Following a positive ctDNA result, the proportion of oncologists recommending AC (p < 0.01) and recommending oxaliplatin-based doublet (p < 0.01) increased in all vignettes. Following a negative result, the proportion recommending AC decreased in all intermediate and high-risk vignettes (p < 0.01). Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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14 pages, 1030 KiB  
Article
The Real-Life Impact of mFOLFIRI-Based Chemotherapies on Elderly Patients—Should We Let It or Leave It?
by Balázs Pécsi and László Csaba Mangel
Cancers 2023, 15(21), 5146; https://doi.org/10.3390/cancers15215146 - 26 Oct 2023
Cited by 2 | Viewed by 673
Abstract
Aim: The oncologic treatment of elderly patients is going on with a lack of evidence due to their underrepresentation in clinical trials. Many data suggest that certain groups of elderly patients, like their younger counterparts, may benefit from the systemic treatment of their [...] Read more.
Aim: The oncologic treatment of elderly patients is going on with a lack of evidence due to their underrepresentation in clinical trials. Many data suggest that certain groups of elderly patients, like their younger counterparts, may benefit from the systemic treatment of their metastatic colorectal tumors (mCRC). Method: We performed retrospective data analysis to investigate the clinical course of care and clinical outcomes of 515 patients who received first-line mFOLFIRI-based chemotherapy for mCRC between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs, focusing on a comparison of patients over and under 70 years of age, defined as the cut-off value. Results: 28.7% of the 515 patients were 70 years old and older (median age 73.5 years). Compared to the data of the elderly patients, the younger group (median age 61.1 years) had a performance status that was significantly better (average ECOG 1.07 vs. 0.83, p < 0.0001), and significantly more patients received molecularly targeted agents (MTA) (21.6% vs. 51.8%, p < 0.0001); nevertheless, mPFS (241 vs. 285 days, p = 0.3960) and mOS (610 vs. 698 days, p = 0.6305) results did not differ significantly. Considering the 1y PFS OR and the 2ys OS OR values (0.94 [95%CI 0.63–1.41] and 0.72 [95%CI 0.47–1.09], respectively), only a non-significant trend was observed in OS favouring the younger population. Additional analysis of our data proved that the survival in patients over 70 years was positively affected by the addition of MTAs to the doublet chemotherapies, and the reasonable modifications/reductions in dose intensity and the addition of local interventions had similar positive effects as observed in the younger patients’ group. Conclusions: Age stratification of mCRC patients is not professionally justified. Patients over 70 years of age with good performance status and controlled co-morbidities benefit from systemic therapy, its modifications and local treatment to the same extent as younger patients. With the increasing incidence of age-related cancers due to the rising average lifespan, prospective randomised clinical trials are needed to determine the real value of systemic therapy in the elderly and the rational, objective methods of patient selection. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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38 pages, 1362 KiB  
Review
Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets
by Nikolay Shakhpazyan, Liudmila Mikhaleva, Arkady Bedzhanyan, Zarina Gioeva, Nikolay Sadykhov, Alexander Mikhalev, Dmitri Atiakshin, Igor Buchwalow, Markus Tiemann and Alexander Orekhov
Biomedicines 2023, 11(9), 2361; https://doi.org/10.3390/biomedicines11092361 - 23 Aug 2023
Viewed by 1647
Abstract
Colorectal cancer (CRC) is a major health burden worldwide and is the third most common type of cancer. The early detection and diagnosis of CRC is critical to improve patient outcomes. This review explores the intricate interplay between the tumor microenvironment, stromal interactions, [...] Read more.
Colorectal cancer (CRC) is a major health burden worldwide and is the third most common type of cancer. The early detection and diagnosis of CRC is critical to improve patient outcomes. This review explores the intricate interplay between the tumor microenvironment, stromal interactions, and the progression and metastasis of colorectal cancer. The review begins by assessing the gut microbiome’s influence on CRC development, emphasizing its association with gut-associated lymphoid tissue (GALT). The role of the Wnt signaling pathway in CRC tumor stroma is scrutinized, elucidating its impact on disease progression. Tumor budding, its effect on tumor stroma, and the implications for patient prognosis are investigated. The review also identifies conserved oncogenic signatures (COS) within CRC stroma and explores their potential as therapeutic targets. Lastly, the seed and soil hypothesis is employed to contextualize metastasis, accentuating the significance of both tumor cells and the surrounding stroma in metastatic propensity. This review highlights the intricate interdependence between CRC cells and their microenvironment, providing valuable insights into prospective therapeutic approaches targeting tumor–stroma interactions. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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15 pages, 11600 KiB  
Article
Clinicopathologic Significance of Heat Shock Protein 60 as a Survival Predictor in Colorectal Cancer
by Myunghee Kang, Soyeon Jeong, Jungsuk An, Sungjin Park, Seungyoon Nam, Kwang An Kwon, Debashis Sahoo, Pradipta Ghosh and Jung Ho Kim
Cancers 2023, 15(16), 4052; https://doi.org/10.3390/cancers15164052 - 11 Aug 2023
Cited by 1 | Viewed by 1091
Abstract
The role of heat shock protein 60 (HSP60), a mitochondrial chaperone, in tumor progression or its anti-tumor effects remains controversial. This study aimed to confirm the possibility of using HSP60 as a prognostic marker in patients with colorectal cancer (CRC), considering TNM classification [...] Read more.
The role of heat shock protein 60 (HSP60), a mitochondrial chaperone, in tumor progression or its anti-tumor effects remains controversial. This study aimed to confirm the possibility of using HSP60 as a prognostic marker in patients with colorectal cancer (CRC), considering TNM classification for precise prediction. HSP60 expression increased with differentiation and p53 mutations in patients. However, compared to patients with high HSP60 expression, patients with low HSP60 expression had event-free survival and disease-specific survival hazard ratios (HRs) of 1.42 and 1.69, respectively. Moreover, when the survival rate was analyzed by combining TNM classification and HSP60 expression, the prognosis was poor, particularly when HSP60 expression was low in the late/advanced stage. This pattern was also observed with HSP family D member 1, HSPD1, the gene that encodes HSP60. Low HSPD1 expression was linked to lower overall survival and relapse-free survival rates, with HRs of 1.80 and 1.87, respectively. When TNM classification and HSPD1 expression were considered, CRC patients with low HSPD1 expression and advanced malignancy had a poorer prognosis than those with high HSPD1 expression. Thus, HSPD1/HSP60 can be a useful biomarker for a sophisticated survival prediction in late- and advanced-stage CRC, allowing the design of individualized treatment strategies. Full article
(This article belongs to the Topic Advances in Colorectal Cancer Therapy)
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