Search Results (4,029)

Background/Objectives: Chronic inflammation is a key factor in the development and progression of colorectal cancer (CRC). When COX-2 levels and PGE₂ production increase, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA) and selective COX-2 inhibitors, such as celecoxib and rofecoxib, are commonly employed. This paper presents the effect of anti-inflammatory drugs, primarilyNSAIDs, on the incidence of CRC. Methods: A comprehensive literature search (119 articles) was conducted with databases such as PubMed. During our research, we used keywords such as colorectal cancer (CRC), nonsteroidal anti-inflammatory drugs (NSAIDs), ASA, COX, precision oncology, and personalized medicine. Results: The development of CRC is primarily associated with chronic inflammation and the actions of COX-2 and prostaglandin E2 (PGE₂), which promote cancer cell proliferation and angiogenesis. Anti-inflammatory drugs act by inhibiting the secretion of COX-1 and COX-2 enzymes, which leads to reduced PGE₂ production and may limit tumor growth. Aspirin has the best-documented and studied anti-cancer effect; long-term use is associated with a reduced risk of CRC development and mortality through its anti-inflammatory and antiplatelet effects, thereby limiting metastasis. Particularly beneficial effects are observed in patients with mutations in the PIK3CA gene. Factors influencing the effectiveness of CRC treatment include molecular differences and tumor location. Conclusions: The future of CRC treatment and prevention lies in personalized medicine, which accounts for each patient’s genetic profile. Decisions regarding NSAIDs use and CRC prevention should consider the potential benefits and risks of side effects. Full article

Colorectal cancer (CRC) and non-Hodgkin lymphoma (NHL) are among the most prevalent cancer types globally by incidence and mortality. Both types are influenced differentially by chronic inflammation. Central to this inflammation are inflammatory genes that are meticulously regulated by nuclear factor kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). NF-κB is negatively regulated by IκBα (encoded by NFKBIA), while TNF-α’s actions can be modulated by ghrelin (encoded by GHRL). We investigated four single nucleotide polymorphisms (SNPs) in NFKB1 (rs4648068), NFKBIA (rs2233406), TNF-α (rs1800629), and GHRL (rs1629816) as biomarkers for CRC and NHL risk in a cohort of Kuwaiti individuals. DNA samples from patients and controls were collected and genotyped for all SNPs, and their association with CRC or NHL risk was assessed. While rs4648068 showed a modest association with increased CRC risk, it had no significant impact on NHL risk. Conversely, rs2233406 increased NHL risk without affecting CRC risk. Interestingly, while rs1800629 showed a protective effect against NHL, it showed an increased risk for CRC. Finally, rs1629816 was associated with greater NHL but not CRC risk. Our findings suggests that variations of these inflammatory genes may be useful indicators for predicting cancer risk but might have unpredictable effects on cancer susceptibility, depending on the cancer type. Full article

Precision medicine is increasingly applied in the cancer clinic, adapting treatment to genomic alterations of the tumor. However, whether alterations disrupt the function of a protein can depend on if both alleles of a gene are altered. While massively parallel sequencing technologies can identify sequence aberrations, they are limited in resolving the corresponding haplotype information. In this proof-of-concept case study, we applied the linked-read droplet barcode sequencing (DBS) technology to resolve the haplotype complexity of colorectal cancer genomes on paired tumor and normal samples. Several cancer-related genes carried multiple mutations in either one or both haplotypes. Additionally, a number of haplotype-resolved large structural variants and copy number alterations were detected and phased with short somatic variants. Nearly all characterized oncogenic pathways harbored some of the identified short somatic variants. The study demonstrates that linked-read DBS technology can characterize complex genetic variations in a haplotype context and may provide essential information for personalized approaches. Full article

CRC remains a major cause of cancer-related morbidity and mortality worldwide. In recent years, the gut microbiota has gained increasing attention in CRC research. Intestinal microbes are not passive bystanders in tumor development. They may promote persistent inflammation, disrupt epithelial barrier integrity, alter microbial metabolites, and affect host immune and signaling pathways. Emerging evidence also suggests that microbiota-related metabolites and microbial functional alterations may influence host epigenetic regulation, including DNA methylation and chromatin-associated signaling, thereby further shaping colorectal carcinogenesis. Together, these changes can create a microenvironment that favors tumor initiation and progression. Several bacterial species, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius, have been repeatedly associated with CRC. In contrast, beneficial commensal microbes and their metabolites, especially short-chain fatty acids, may help maintain intestinal homeostasis and limit tumor-promoting processes. Because the gut microbiota is strongly shaped by diet, lifestyle, and environmental exposure, regional differences are also relevant. This is particularly important in Sichuan, China, where distinctive dietary habits and environmental features may influence microbial patterns associated with CRC risk and disease behavior. This review summarizes the main mechanisms linking the gut microbiota to CRC, examines the regional context of Sichuan, China, and discusses current and emerging clinical strategies. These include dietary intervention, probiotics, fecal microbiota transplantation, and microbiome-informed approaches to prevention, diagnosis, and treatment. Full article

Background: Colorectal cancer is a common malignancy and 5-fluorouracil (FU) remains a mainstay of chemotherapy despite its toxicity. As an important part of comprehensive tumor treatment, dual-protein (DP) nutritional intervention is attracting more and more attention. Methods: This study preliminarily evaluated the regulatory effects of DP intervention on colorectal cells of CT26 tumor-bearing mice, examining the dosage and administration methods of DP, as well as the anti-tumor effects of FU alone or in combination with DP. Results: The results showed that low- and medium-dose DP numerically increased spleen index and showed trends toward alleviating FU-induced thymic atrophy, splenic damage, nephrotoxicity, and myocardial injury. It also partly mitigated muscle wasting, prevented FU-induced shortening of the colorectal tract, and reduced intestinal injury. In addition, DP was associated with increased lymphocyte, monocyte, and platelet counts and decreased granulocytes, suggesting possible alleviation of chemotherapy-induced bone marrow suppression and a potential effect on hematopoietic function. Flow cytometry results indicated possible effects of DP on CD4⁺ T and CD8⁺ T cell proliferation or apoptosis, modulation of effector and memory phenotypes, reduced splenic neutrophil levels, balanced B cell function, and maintained natural killer cell activity. In addition, DP intervention also showed trends toward regulating hepatic lipid metabolism and partially alleviating FU-induced dyslipidemia and muscle damage. In addition, DP and FU could increase IL-2, IL-10, GM-CSF and IFN-γ and decrease IL-6 and TNF-α. Conclusion: In conclusion, a moderate dose (0.67 g/kg) of DP had the most favorable trends, and the pre-intervention mode was more effective. This study also provided exploratory data on the potential of DP in reducing chemotherapy-related toxicity. These findings will provide preliminary scientific support for nutritional therapy in colorectal cancer patients, as well as for the research, development, and application of dual-protein foods for special medical purposes. Full article

With colorectal cancer (CRC) accounting for over 1.9 million new cases and 930,000 deaths globally in 2020, there is a critical need for innovative indicators to forecast disease advancement and therapeutic outcomes. The gut microbiome has emerged as a fertile area for discovering such diagnostic and prognostic signals. This narrative review collected current evidence on intestinal microorganisms and their metabolic products as candidate markers for CRC control. Intestinal communities influence malignancy through diverse mechanisms, including metabolic shifts, immune modulation, inflammation, proliferation/apoptosis regulation, genotoxicity, and mucosal barrier disruption. Pathogenic species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis, facilitate tumorigenesis via FadA-mediated signaling and Th17/IL-17 responses. In contrast, beneficial taxa like Faecalibacterium prausnitzii and Akkermansia muciniphila provide protective effects through short chain fatty acid production. Macrophage phenotype physiological equilibrium is altered and inflammatory status fluctuates under the former. Metabolically, hydrogen sulfide damages mitochondrial DNA and secondary bile acids stimulate cellular proliferation. While 16S rRNA sequencing and shotgun metagenomics are established detection strategies, innovative platforms like organoids and gene arrays remain in the exploratory stage. Clinical data indicates that F. nucleatum aligns with advanced tumor stage, and its combined detection with colibactin-producing E. coli achieves high sensitivity for early-stage screening. Additionally, A. muciniphila levels can anticipate the efficacy of PD-1 blockade immunotherapy. Microbiota-derived tools represent a transformative direction in oncology. Future research must focus on standardizing protocols and validating multi-marker panels to enhance clinical translation. Full article

Background: Persistent lymph node metastases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer indicate poor response to treatment. This study evaluated the long-term prognosis of patients with residual nodal disease following neoadjuvant RCT and total mesorectal excision (TME) in comparison with patients who underwent upfront TME without adjuvant radiotherapy. Methods: Consecutive patients with rectal adenocarcinoma and histopathologically confirmed lymph node metastases after TME were identified from the prospectively maintained database of the colorectal unit at Dresden-Friedrichstadt General Hospital. Patients with distant metastases, in-hospital mortality, or postoperative radiotherapy were excluded. The two groups were comprehensively compared regarding patient-, tumor-, and treatment-related characteristics. Cumulative local recurrence, time to recurrence, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method. Results: Between 1996 and 2021, 155 eligible patients were identified, including 101 patients in the RCT group and 54 in the upfront surgery group. Baseline characteristics were largely comparable, except for a higher median age (70.5 vs. 64 years, p < 0.001) and a higher proportion of lymphovascular invasion (36.0% vs. 15.2%, p = 0.004) in the upfront surgery group. Ten-year local recurrence rates were similar between groups (21.0% [95% CI: 10.4–31.6] vs. 20.8% [95% CI: 8.5–33.1], p = 0.609). No significant differences were observed in time to recurrence or cancer-specific survival. Overall survival was lower in the upfront surgery group, most likely reflecting the substantially higher age of these patients. Conclusions: Despite more intensive treatment, patients with a persistent ypN-positive category have outcomes no better than untreated patients with node-positive disease after TME, indicating a biologically high-risk subgroup. Non-response is therefore a sign of a negative selection. These patients may lose the opportunity for optimal local tumor control during prolonged neoadjuvant treatment, underscoring the urgent need for reliable predictive markers to identify non-responders and guide individualized treatment strategies. Full article

Background/Objectives: Colorectal cancer (CRC) represents a major public health problem in Mexico and is among the malignancies with the highest morbidity and mortality. Alterations in TP53 are frequent molecular events in tumors with chromosomal instability; however, information on TP53 variants in the Mexican population, particularly in exons 4-8, remains limited. Exons 4-8 comprise the main coding region of the p53 DNA-binding domain; therefore, this study aimed to identify TP53 variants in these regions and evaluate p53 protein expression by immunohistochemistry in sporadic CRC. Methods: Tumor samples from 142 patients who underwent surgical resection without neoadjuvant treatment were analyzed. DNA was extracted from tumor tissue. TP53 exons 4-8 were amplified by polymerase chain reaction (PCR), and variants were identified by Sanger sequencing. p53 immunohistochemistry was performed in 40 tumors and 36 adjacent tissues, and nuclear expression was assessed using the Immunoreactivity Score. Results: Forty-three heterozygous variants were identified in 106/142 patients, representing 75% of the cohort. Thirty-one patients carried oncogenic variants, mainly clustered within the DNA-binding domain and involving hotspot residues such as Arg175, Tyr220, Gly245, Arg248, Arg273, and Arg282. Nuclear p53 expression was observed in 9/40 tumors, whereas all adjacent tissues were negative. Conclusions: TP53 alterations in exons 4-8 are frequent and heterogeneous in this Mexican cohort. Integrating mutational profiling with p53 immunohistochemistry provides complementary information for the biological interpretation of these tumors, including variants of translational interest. Full article

Background/Objectives: Body-surface-area-based dosing of continuous-infusion 5-fluorouracil does not account for inter-individual pharmacokinetic variability. This pilot study explored whether patient-level representative plasma 5-fluorouracil exposure within the target area under the concentration–time curve (AUC) range was associated with clinical outcomes. It evaluated a prototype immunochromatographic assay as a preliminary monitoring tool. Methods: Fifteen patients with unresectable advanced or recurrent colorectal cancer who received continuous-infusion 5-fluorouracil-based chemotherapy were prospectively evaluated between 1 January 2017 and 30 April 2018. Plasma 5-fluorouracil levels were measured during eight treatment cycles at three time points in each cycle. Representative AUC values were calculated using median concentrations across cycles and interpreted as exploratory patient-level exposure indices. Tumor response, grade ≥2 adverse events, progression-free survival, and overall survival were assessed descriptively. Results: The median representative AUC was 24.3 mg·h/L. Eight patients (53.3%) were within the target range of 20–30 mg·h/L, whereas seven (46.7%) were outside it. Disease control was observed in 7 of 8 patients (87.5%) within the target range and in 3 of 7 patients (42.9%) outside it. Grade ≥2 adverse events were less frequent in the target-range group (2/8, 25.0%) than in the outside-range group (6/7, 85.7%; p = 0.041). Progression-free survival was numerically longer in the target-range group (17.2 vs. 9.2 months, p = 0.36), while overall survival did not differ clearly (p = 0.76); these survival analyses were exploratory. The prototype immunochromatographic assay showed a favorable correlation with the My-5FU assay (R2 = 0.762), but Bland–Altman analysis showed relatively wide limits of agreement. Conclusions: Target plasma 5-fluorouracil exposure was associated with lower clinically relevant toxicity and may support favorable tumor control in this pilot cohort. The prototype immunochromatographic method demonstrated preliminary feasibility for rapid plasma 5-FU monitoring but requires further validation before routine dose adjustment. Full article

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy and the second leading cause of cancer-related mortality worldwide, underscoring the need for the development of more effective and durable therapeutic strategies. A key mechanism of tumor immune evasion involves activation of immune checkpoint pathways through the upregulation of inhibitory ligand expression within the tumor microenvironment, leading to lymphocyte exhaustion and impaired antitumor immunity. Consequently, immune checkpoints have emerged as important targets for immunotherapeutic intervention, with significant advances over the past decade. Nevertheless, despite demonstrated clinical benefits in selected patient subpopulations, the overall therapeutic efficacy of immune checkpoint inhibitors remains limited, particularly in the context of CRC. In this review, we provide a comprehensive overview of currently approved immune checkpoint-based immunotherapies for cancer treatment, with a specific focus on CRC, as well as ongoing clinical trials and evolving trends in this area. Furthermore, we discuss emerging targets and novel therapeutic strategies, with particular emphasis on innovative small-molecule inhibitors as potential alternatives to monoclonal antibody-based approaches. Finally, we outline future perspectives and potential directions for advancing immune checkpoint-targeted therapies in CRC. Full article

Background: Human epidermal growth factor receptor 2 (HER2) alterations have been implicated as mechanisms of resistance to anti-epidermal growth factor receptor (anti-EGFR) therapy in metastatic colorectal cancer (mCRC). We aimed to evaluate the predictive and prognostic significance of HER2 expression in patients with RAS wild-type mCRC in a real-world setting. Methods: We conducted a multicenter retrospective cohort study across ten oncology centers in Turkey, including patients with RAS wild-type mCRC treated between 2015 and 2022. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between HER2-positive and HER2-negative groups. Multivariable Cox proportional hazards models were used to identify independent predictors of survival outcomes. Results: Among 204 patients, 28 (13.7%) were HER2-positive. Baseline characteristics were generally comparable; however, HER2-positive patients showed a trend toward higher-grade tumors and were significantly less likely to receive anti-EGFR therapy. HER2-positive patients had significantly shorter PFS compared to HER2-negative patients (median 10 vs. 13 months; p = 0.006). In multivariable analysis, HER2 positivity remained an independent predictor of shorter PFS (HR 1.76, 95% CI 1.01–3.07; p = 0.045). In the subgroup of 144 patients receiving anti-EGFR therapy, HER2-positive patients also demonstrated significantly shorter PFS (median 9.0 vs. 14.0 months; p = 0.023). No significant differences in OS were observed between groups. Conclusions: HER2 positivity is associated with reduced response to anti-EGFR therapy and independently predicts shorter PFS in patients with RAS wild-type mCRC. These findings further support the role of HER2 as a clinically relevant biomarker in RAS wild-type mCRC, particularly in predicting response to anti-EGFR therapy, while highlighting the need for optimized patient selection strategies in the era of HER2-targeted treatments. Full article

Activation of signal transducer and activator of transcription 3 (STAT3) is implicated in tumor progression and correlates with poor prognosis and reduced survival. In colorectal cancer (CRC), STAT3 activation serves as a key indicator of unfavorable outcomes. However, the scarcity of clinically available STAT3 inhibitors hinders the development of personalized treatment strategies targeting STAT3. Therefore, we aimed to develop a novel STAT3 inhibitor based on the molecular structure of STAT3 and our previously reported STAT3 inhibitor LY17 to inhibit the progression of CRC. The binding of the novel STAT3 inhibitor DB-2B to STAT3 was confirmed by computational docking, surface plasmon resonance, isothermal titration calorimetry, and cellular thermal shift assays. Western blotting and immunofluorescent staining demonstrated that DB-2B specifically inhibited STAT3 activation and nuclear translocation. In vitro studies revealed that DB-2B significantly suppressed proliferation, induced apoptosis, arrested cell cycle progression, and attenuated stemness by inhibiting STAT3 activation and its downstream signaling pathways. In vivo, DB-2B exhibited favorable oral bioavailability and safety, while significantly inhibiting the progression of CRC. Collectively, this study presents DB-2B as a promising small-molecule STAT3 inhibitor for the targeted treatment of CRC. Full article

Background/Objectives: The triglyceride–glucose (TyG) index, a reliable marker for insulin resistance, is strongly associated with T2DM, hypertension, and cardiovascular disease. Less well known is its relationship with cancer risk. The aim of this study was to quantify the association between the TyG index and risk of different types of cancer. Methods: Publications were searched in the PubMed, Web of Science, and Scopus databases using appropriate keywords. The PICOS framework was used to select the studies, and their quality was evaluated according to the “Newcastle–Ottawa Scale” (NOS). Meta-analysis was performed through a random-effects model using cancer risk parameters (RR: relative risk, OR: odds ratio and HR: hazard ratio) extracted from 26 selected studies associated with TyG index values. The weighted mean difference (WMD) was used to compare the mean of the TyG index in cancer patients to that of the control group. Heterogeneity was assessed by Cochran’s Q and I² statistics, while publication bias was evidenced using the Egger test and the Begg test, and funnel plot asymmetry. Results: A higher TyG index value was observed in cancer subjects (9483) compared to healthy controls (978,675) (WMD: 0.23, 95% CI: 0.16–0.31, p < 0.0001, n = 15). A statistically significant increase in cancer risk was associated with the TyG index level, expressed as both a categorical (OR 1.33, 95% CI 1.22–1.45, p < 0.0001, n = 29) and continuous (OR 1.14, 95% CI 1.10–1.19, p < 0.0001, n = 27) variable. The effect was more evident in case–control/cross-sectional studies compared to cohort studies (OR 1.78, 95% CI 1.51–2.09 vs. OR 1.19, 95% CI 1.10–1.29 TyG categorical; OR 1.46, 95% CI 1.21–1.76 vs. OR 1.09, 95% CI 1.05–1.12 TyG continuous). Stratified analysis showed an increased risk of cancer occurrence for gastrointestinal, gynecological, colorectal, breast, and gastric sites, while no association was observed for endometrial, ovarian, prostate, lung or esophageal cancers. Conclusions: Our results evidence an increase in cancer risk associated with higher TyG index values. However, due to the low number of studies, the effect on specific tumor sites was not statistically significant. Additional epidemiological studies with a cohort design are necessary to confirm these associations. Full article

Background: Microsatellite instability (MSI) is an important biomarker for the diagnosis of Lynch syndrome and for guiding immunotherapy in various solid tumors. Droplet digital PCR (ddPCR) has emerged as a highly sensitive method for detecting MSI, particularly in circulating tumor DNA (ctDNA). This study aimed to evaluate the analytical and clinical performance of a ddPCR assay using three MSI markers (BAT-26, ACVR2A, and DEFB105A/B) in colorectal, gastric, and endometrial cancers. Methods: Formalin-fixed paraffin-embedded (FFPE) samples from 190 patients (83 colorectal, 44 gastric, and 63 endometrial cancers) and 21 plasma samples from patients with metastatic solid tumors were analyzed. MSI status determined by ddPCR was compared with conventional PCR using a pentaplex panel and immunohistochemistry (IHC). Analytical performance, including limit of blank (LoB) and limit of detection (LoD), was evaluated using cell line DNA, and clinical cut-offs were established using receiver operating characteristic analysis. Results: The ddPCR assay demonstrated high analytical sensitivity, with LoD values of 0.075% for BAT-26, 0.1% for ACVR2A, and 0.025% for DEFB105A/B. Using optimized clinical cut-offs, the concordance rate between ddPCR and conventional PCR assays was 98.4% in tissue samples. Marker performance varied by cancer type, with reduced sensitivity observed in endometrial cancer. In plasma samples, MSI-H was detected in 1 of 21 cases (4.8%), and the overall concordance rate with tissue-based MSI status was 94.7%. Conclusions: The ddPCR assay demonstrated high concordance with conventional MSI testing methods and showed potential as a sensitive tool for MSI detection in both tissue and plasma samples. However, optimization of marker panels and establishment of sample-type-specific clinical cut-offs are required, particularly for ctDNA-based analysis. Further large-scale studies are needed to validate the clinical utility of ddPCR for MSI detection and monitoring. Full article

Background: Aspirin, initially recognized for its anti-inflammatory, antipyretic and analgesic properties, holds a prominent role in the treatment of cardiovascular disease. The utility of aspirin in cancer therapeutics has been explored and stratified into COX-dependent and -independent mechanisms. COX2 gene expression has been demonstrated to be significantly upregulated in colorectal cancer and various other gastrointestinal malignancies including pancreatic, esophageal, and gastric cancer. This study investigates the relationship of aspirin use and outcomes in patients with colorectal cancer. Methods: The Nationwide Inpatient Sample (NIS) database from 2017 to 2022 was analyzed for patients age > 18 who were hospitalized for colorectal cancer and its decompensations using ICD-10 diagnostic codes. These patients were further stratified based on the long-term use of aspirin. The principal outcome of this investigation are the odds of in-hospital mortality, with secondary outcomes including odds of pulmonary embolism, portal vein thrombosis, acute kidney injury, septic shock, requiring an ICU level of care and odds of hepatic, pulmonary, gastrointestinal and peritoneal or retroperitoneal metastatic disease. Multivariate logistic regression accounting for hospital and patient characteristics was implemented for analysis, with the Charlson Comorbidity Index used to adjust for coexisting comorbidity burden; a p-value (p) of <0.05 was considered statistically significant. Results: In our analysis of the NIS, 596,160 patients were identified with colorectal cancer and 11.7% (69,750) of this population were identified with long-term use of aspirin. Aspirin use was identified to have a significantly reduced odds of in-patient mortality (adjusted odds ratio) [aOR] 0.530, p value < 0.001 95% CI (confidence interval): 0.460–0.617. Patients with aspirin use also demonstrated significantly reduced odds of adverse outcomes and gastrointestinal, hepatic, pulmonary and retroperitoneal/peritoneal metastasis; (aOR 0.606, 95% CI: 0.564–0.653, p < 0.001), (aOR 0.628, 95% CI: 0.582–0.678, p < 0.001), (aOR 0.676, 95% CI: 0.605–0.755, p < 0.001) and (aOR 0.751, 95% CI: 0.685–0.825, p < 0.001) respectively. Conclusions: In recent years, there has been an alarming increase in incidence of colorectal cancer, particularly amongst younger individuals with increased associated mortality. This mortality increase, albeit alarming, is a driving force for treatment innovation with continual examination of our repertoire of medications for possible repurposed applications. COX2-mediated signaling serves as a key promotor of tumorigenic molecular signaling that directly contributes to tumor cell proliferation, angiogenesis and metastasis in colorectal cancer. Aspirin use and its inhibitory action on COX2 demonstrated a significantly reduced odds of in-hospital mortality. Aspirin use is also associated with significantly reduced odds of developing metastatic disease to the liver, gastrointestinal system, lungs and peritoneum in patients with colorectal cancer. These findings convey that aspirin use reduces the likelihood of in-hospital mortality, major comorbid conditions and of developing metastatic disease as compared to those who do not use aspirin. Full article