Search Results (163)

Background: Colorectal cancer (CRC) is a prevalent gastrointestinal malignancy, ranking third in incidence and second in cancer-related mortality. Despite therapeutic advances, challenges such as chemotherapy toxicity and drug resistance persist. Thus, there is an urgent need for novel CRC treatments. However, developing new drugs is time-consuming and resource-intensive. As a more efficient approach, drug repurposing offers a promising alternative for discovering new therapies. Methods: In this study, we screened 1068 small molecular compounds from an FDA-approved drug library in CRC cells. Menadione was selected for further study based on its activity profile. Mechanistic analysis included a cell death pathway PCR array, differential gene expression, enrichment, and network analysis. Gene expressions were validated by RT-qPCR. Results: We identified menadione as a potent anti-tumor drug. Menadione induced three programmed cell death (PCD) signaling pathways: necroptosis, apoptosis, and autophagy. Furthermore, we found that the anti-tumor effect induced by menadione in CRC cells was mediated through a key gene: MAPK8. Conclusions: By employing methods of cell biology, molecular biology, and bioinformatics, we conclude that menadione can induce multiple forms of PCD in CRC cells by activating MAPK8, providing a foundation for repurposing the “new use” of the “old drug” menadione in CRC treatment. Full article

Background: Bulgaria carries a high burden of colorectal cancer (CRC) but, at the start of this study, lacked a nationwide organized screening program. Understanding specialist views (particularly on mail-based fecal testing) is essential for effective policy development. Objective: The objective is to assess the attitudes towards, practices of, and perceived barriers to CRC screening among Bulgarian gastroenterologists, with a focus on the feasibility of mail-based fecal occult blood testing (FOBT). Methods: A cross-sectional survey of 38 gastroenterologists examined clinical use of FOBT, screening method preferences, and perceived systemic and patient-level barriers to CRC screening. Results: Among respondents, 57.89% reported using FOBT in clinical practice, and 71.05% indicated they would undergo the test themselves and recommend it to relatives. Colonoscopy was the preferred diagnostic tool for 84.21% of participants; however, the existing literature raises concerns about its feasibility for large-scale population screening. Key systemic barriers, rated on a 5-point Likert scale, included financial constraints (mean = 3.08), inadequate infrastructure (2.89), and healthcare workforce shortages (2.71). Patient-level barriers were led by low health literacy (4.13), lack of motivation (3.95), and procedural fears (3.26). A majority (84.38%) believed that mail-based FOBT would increase screening uptake, and 57.89% supported annual distribution of test kits. Nearly all respondents (97.37%) favored initiating screening at age 50. Conclusions: This study highlights strong support among Bulgarian gastroenterologists for a national CRC screening program, with particular endorsement of mail-based FOBT. Despite acknowledged systemic and population-level barriers, the findings suggest that such an approach could increase screening coverage, promote early detection, and support the strategic rollout of Bulgaria’s emerging cancer control initiatives. Full article

Background/Objectives: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Even though the screening programs have decreased the incidence rates, the prognosis for CRC varies depending on the stage at diagnosis. Thus, early diagnosis is still a big challenge due to screening methods, and subsequent diagnosis is not very sensitive. Methods: In this work, LC-MS-based metabolomics, a powerful and sensitive tool to study complex dynamic changes, was used to analyze 211 human fecal samples from control individuals (CTRL), adenoma (AA), and CRC patients. Results: Multivariate and univariate statistical analysis highlighted cholesteryl esters (CEs) and fecal haemoglobin, quantified by fecal immunochemical test (FIT), as relevant biomarkers that clearly differentiate CRC from AA and CTRL. Predictive models based on random forest and the area under the curve (AUC) of the receiver operating characteristic curve (ROC) demonstrate that CEs, together with FIT measurement, improved the CRC and CTRL classification, but not AA. This study revealed that the AA group is a transitional stage with high heterogeneity. The increased tendency observed in CEs from CTRL to CRC might be related to the imbalance of cholesterol homeostasis due to cancer cells requiring a high cholesterol level for cell development and proliferation. The free cholesterol is probably obtained from CEs, as it is the most cost/effective way to obtain the needed cholesterol. Conclusions: The accumulation of CEs is produced by two possible approaches: (1) dysfunction of cholesterol absorption in the small intestine and/or (2) transported inside exosomes from cell to cell to promote proliferation. Full article

In November 2024, the fourth annual Symposium focusing on early-age onset cancer (EAOC) was hosted by the Colorectal Cancer Resource & Action Network (CCRAN), assembling clinicians, researchers, and patients virtually to discuss challenges in early detection and diagnosis of individuals afflicted with EAOC across tumour types. The meeting addressed the rising rates of EAOC and identified strategies to overcome barriers to timely detection and diagnosis by closing gaps in public and healthcare provider knowledge on symptoms of cancer in younger adults and reducing inequities in standard screening for younger age groups. Discussions also encompassed the various factors that serve as impediments to accessing diagnostic testing and obtaining results, as well as the critical need for access to diagnostics such as comprehensive genomic profiling (CGP), the results of which could be imperative in helping to guide clinical decisions regarding effective and well-tolerated targeted therapies. The Symposium generated key calls to action regarding increasing EAOC education and awareness among primary care providers and the public, re-evaluation of cancer screening programs’ eligibility criteria to include younger populations, and mechanisms to reduce waiting times for diagnostic testing by addressing technologist shortages and improving access to CGP through national collaborative strategies and increased funding. Full article

Background: Prehabilitation programs improve postoperative outcomes in vulnerable patients undergoing major surgery. However, current screening tools such as the Malnutrition Universal Screening Tool (MUST) may lack the sensitivity needed to identify those who would benefit most. Muscle quality assessed by Computed Tomography (CT), specifically muscle radiodensity in Hounsfield Units (HUs), has emerged as a promising alternative for risk stratification. Objective: To evaluate the prognostic performance of CT-derived muscle radiodensity in predicting adverse postoperative outcomes in colorectal cancer patients, and to compare it with the performance of the MUST score. Methods: This single-center cross-sectional study included 201 patients with non-metastatic colon cancer undergoing elective laparoscopic resection. Patients were stratified based on enrollment in a multimodal prehabilitation program, either within an Enhanced Recovery After Surgery (ERAS) protocol or a non-ERAS pathway. Nutritional status was assessed using MUST, SARC-F questionnaire (strength, assistance with walking, rise from a chair, climb stairs, and falls), and the Global Leadership Initiative on Malnutrition (GLIM) criteria. CT scans at the L3 level were analyzed using automated segmentation to extract muscle area and radiodensity. Postoperative complications and hospital stay were compared across nutritional screening tools and CT-derived metrics. Results: MUST shows limited sensitivity (<27%) for predicting complications and prolonged hospitalization. In contrast, CT-derived muscle radiodensity demonstrates higher discriminative power (AUC 0.62–0.69), especially using a 37 HU threshold. In the non-ERAS group, patients with HU ≤ 37 had significantly more complications (33% vs. 15%, p = 0.036), longer surgeries, and more severe events (Clavien–Dindo ≥ 3). Conclusions: Opportunistic CT-based assessment of muscle radiodensity outperforms traditional screening tools in identifying patients at risk of poor postoperative outcomes, and may enhance patient selection for prehabilitation strategies like the ERAS program. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality worldwide, posing a substantial health and economic burden. Despite advances in screening and treatment, significant socioeconomic and healthcare-related disparities persist across European Union (EU) member states. This study aims to identify trends and inequality in CRC burden over time and to explore the relationship between country-level socioeconomic and healthcare indicators and CRC burden across EU member states. Methods: Age-standardized mortality, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALY) rates were extracted from Global Burden of Diseases Study 2021 for 24 EU countries. Socioeconomic and healthcare indicators were extracted from Eurostat between 2005 and 2021. The Gini index was calculated to evaluate CRC-related health inequality, and generalized linear mixed models were used to assess the link between indicators and disease burden. Results: The Gini index for age-standardized YLDs declined from 0.19 to 0.12 between 1990 and 2021, while inequality in YLL (from 0.11 to 0.16), DALY (from 0.11 to 0.15), and mortality rates (from 0.12 to 0.14) increased. The number of practicing physicians (p < 0.05) and higher levels of education (p < 0.001) were related to lower death, DALY, YLD, and YLL rates. Conversely, greater income inequality was linked to higher mortality, DALY, and YLL rates (p < 0.05). Conclusions: Our findings underscore that, in addition to expanding organized screening programs, enhancing physician availability and addressing socioeconomic inequalities are essential for reducing the burden of CRC. Full article

Background: Colorectal cancer (CRC), the most common malignancy of the gastrointestinal tract, is the second leading cause of cancer-related deaths worldwide. In this context, investigating low-penetrance gene variants associated with the increased risk of CRC represents a novel and crucial approach to enhancing prevention strategies and clinical surveillance. By focusing on these genetic variants, there is potential for more accurate prediction of individual CRC risk, which could contribute to the refinement of current screening and prophylactic programs. The aim of this case–control study was to explore the association between SIRT1 polymorphisms and CRC risk. Methods: We analyzed three SNPs—rs12778366 (T/C), rs3758391 (C/T), and rs7895833 (A/G)—in the promoter region of the SIRT1 gene, which may influence SIRT1 expression and thus play a role in cancer development. Our study included 200 patients with colorectal adenocarcinoma and 115 controls. Genomic DNA was extracted from blood samples, and SIRT1 SNP analysis was performed using the qPCR method and endpoint genotyping. Results: Univariate regression analysis revealed a slightly increased risk of developing CRC in individuals with minor alleles of the analyzed polymorphisms; however, the observed differences were not statistically significant. Conclusions: Although our findings did not reveal statistically significant differences in SIRT1 gene polymorphism frequencies between the CRC group and the control group, we observed a tendency that suggests further investigation in larger cohorts is warranted. This research underscores the importance of understanding low-penetrance genetic factors in CRC, highlighting their potential to inform more personalized and effective prevention strategies. Full article

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with growing evidence linking risk to lifestyle and dietary factors. However, nutrition-related exposures have rarely been integrated into existing CRC risk prediction models. This study aimed to develop and validate a lifestyle-based 10-year CRC risk prediction model using longitudinal data from a large-scale population-based screening cohort to facilitate early risk stratification and personalized screening strategies. Methods: Data were obtained from 21,358 individuals participating in a CRC screening program in Shanghai, China, with over 10 years of active follow-up until 30 June 2021. Of these participants, 16,782 aged ≥40 years were used for model development, and 4576 for external validation. Predictors were selected using random survival forest (RSF) and elastic net methods, and the final model was developed using Cox regression. Machine learning approaches (RSF and XGBoost) were additionally applied for performance comparison. Model performance was evaluated through discrimination, calibration, and decision curve analysis (DCA). Results: The final model incorporated twelve predictors: age, gender, family history of CRC, diabetes, fecal immunochemical test (FIT) results, and seven lifestyle-related factors (smoking, alcohol use, body shape, red meat intake, fried food intake, pickled food intake, and fruit and vegetable intake). Compared to the baseline demographic-only model (C-index = 0.622; 95% CI: 0.589–0.657), the addition of FIT improved discrimination, and further inclusion of dietary and lifestyle variables significantly enhanced the model’s predictive accuracy (C-index = 0.718; 95% CI: 0.682–0.762; ΔC-index = 0.096, p = 0.003). Conclusions: Incorporating dietary and lifestyle variables improved CRC risk stratification. These findings highlight the value of dietary factors in informing personalized screening decisions and providing an evidence-based foundation for targeted preventive interventions. Full article

Background/Objectives: Colorectal (CRC), breast (BC), and cervical cancer (CC) pose a significant health burden, yet screening programs have been proven to reduce cancer-specific mortality and other non-lethal endpoints. Mobile health (mHealth) technologies can enhance adherence, but effectiveness varies. This scoping review aims to explore mHealth apps for cancer screening developed with community engagement, identifying research approaches and gaps. Methods: A scoping review following PRISMA-ScR guidelines analyzed studies on mHealth apps for cancer screening developed through community engagement. Community engagement was classified per WHO’s definition. Databases were searched using a PCC-based strategy; eligible studies involved app development, excluding hypothetical apps or text messaging-/social media-only interventions. Screening and data extraction were conducted independently. Results: Thirteen articles were included. Findings indicate a growing but limited body of evidence, with most studies focusing on CRC and BC and involving minority populations through mHealth apps. Key engagement phases included research design, CAB establishment, and recruitment, while priority setting was never community-led. The wMammogram, Meet ALEX, and mMammogram apps improved screening knowledge, intention, and participation, while ColorApp enhanced knowledge but not attitudes. Only CBPR-based studies included dissemination, and one involved the CAB in data analysis. Some studies acknowledged community contributions, though details on ColorApp’s engagement were limited. Conclusions: Standardized engagement frameworks combined with mHealth were associated with greater community involvement and may improve equity. No community-designed mHealth app was found for CC screening, despite its relevance. Future research should address gaps in CC programs, prioritize early community involvement, and assess the long-term impact of mHealth interventions. Full article

Disease progression and treatment resistance in colorectal and other cancers are driven by a subset of cells within the tumor that have stem-cell-like properties and long-term tumorigenic potential. These stem-cell-like cells express the leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) and have characteristics similar to tissue-resident stem cells in normal adult tissues such as the colon. Organoid models of murine and human colorectal and other cancers contain LGR5-expressing (LGR5+) stem-cell-like cells and can be used to investigate the underlying mechanisms of cancer development, progression, therapy vulnerability, and resistance. A large biobank of organoids derived from colorectal cancer or adjacent normal tissue was developed. We performed a large-scale unbiased functional screen to identify bispecific antibodies (BsAbs) that preferentially inhibit the growth of colon tumor-derived, as compared to normal tissue-derived, organoids. We identified the most potent BsAb in the screen as petosemtamab, a Biclonics^® BsAb targeting both LGR5 and the epidermal growth factor receptor (EGFR). Petosemtamab employs three distinct mechanisms of action: EGFR ligand blocking, EGFR receptor internalization and degradation in LGR5+ cells, and Fc-mediated activation of the innate immune system by antibody-dependent cellular phagocytosis (ADCP) and enhanced antibody-dependent cellular cytotoxicity (ADCC) (see graphical abstract). Petosemtamab has demonstrated substantial clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC). The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC. Full article

(1) Background: This study aims to identify the sociodemographic, behavioural, and systemic predictors of colorectal cancer (CRC) screening among primary healthcare attendees in Riyadh, Saudi Arabia, to inform targeted interventions and policy strategies. (2) Methods: This cross-sectional study was conducted between March and July 2023 across 48 randomly selected primary healthcare centers in Riyadh, Saudi Arabia. The target population for this study was adults aged 18 and above attending primary healthcare centers in Riyadh. Multi-stage random sampling was used to recruit participants. Multivariate logistic regression was performed to identify independent predictors of CRC screening. (3) Results: CRC screening uptake was found to be only 4.2%. Age was a significant predictor, with individuals aged 50–75 years (adjusted odds ratio [AOR]: 1.90, 95% confidence interval [CI]: 1.50–2.42) and those aged 75 years or older (AOR: 1.37, 95% CI: 1.01–1.87) being more likely to undergo screening compared to younger individuals. Insurance coverage strongly influenced screening behaviour (AOR: 1.64, 95% CI: 1.37–1.96). Smokers were nearly four times more likely to participate in screening than non-smokers (AOR: 3.87, 95% CI: 3.21–4.69), and physical activity was positively associated with screening (AOR: 1.43, 95% CI: 1.11–1.82). (4) Conclusions: CRC screening uptake in Riyadh is critically low, highlighting the need for targeted public health interventions. Key predictors such as age, insurance coverage, smoking, and physical activity underscore the importance of addressing sociodemographic disparities and promoting health awareness. The findings emphasize the need for culturally tailored educational campaigns, improved healthcare access, and enhanced screening programs to increase uptake. Full article

The implementation of QIs in the pursuit of improving patient outcomes in oncological care has become a primary goal for many countries. The purpose of this cross-sectional review is to present the experiences of several countries that have implemented different strategies in using QIs to assess the quality of cancer care. Countries such as the United States, the United Kingdom, Canada, the Netherlands, Australia, and Israel have been pioneers in integrating QIs into their healthcare systems, which has led to significant improvements in the delivery of care. These indicators help assess adherence to clinical guidelines, timeliness of treatment, safety of practices, and overall patient survival. Data from these countries show that the use of QIs correlates with improved five-year survival rates, earlier diagnosis, better adherence to evidence-based treatment protocols, and increased patient satisfaction. For example, in the Netherlands and Germany, the introduction of quality cancer care programs has led to improved surgical outcomes and overall survival for patients with colorectal cancer. The United Kingdom and Denmark have reported improvements in waiting times for diagnosis and treatment, and in Israel, screening rates for breast and colorectal cancer increased after the introduction of QIs for monitoring these conditions. The current review highlights the fact that countries with robust reporting systems and national cancer registries with high levels of data completeness, such as Denmark, Sweden, and Norway, were able to effectively monitor outcomes and adjust clinical practices accordingly. The findings suggest that implementing QIs in cancer care not only improves clinical outcomes but also promotes accountability and stimulates improved healthcare, ensuring better long-term patient care. This study highlights the value of adopting QIs as a global standard for assessing cancer care. Full article

Background: Compliance with cancer screening guidelines is crucial for the early diagnosis and prevention of cancer. We explored the association of suicidal ideation with participation in cancer screening programs. Methods: This cross-sectional analysis included a nationwide sample consisting of 22,554 Korean adults (9667 men and 12,887 women). Suicidal ideation in the past year was self-reported (yes or no). Participation in gastric, colorectal, cervical, and breast cancer screening within the past 2 years was assessed. Logistic regression models were employed to determine the association of suicidal ideation with participation in each cancer screening test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results: Among men, the participation rates in gastric and colorectal cancer screening were 47.6% and 39.7%, respectively. Among women, the participation rates in gastric, colorectal, cervical, and breast cancer screening were 47.1%, 34.8%, 44.3%, and 50.8%, respectively. In the male sample, suicidal ideation was associated with reduced participation in gastric cancer screening (OR: 0.83, 95% CI: 0.69–0.99) and colorectal cancer screening (OR: 0.82, 95% CI: 0.67–1.00). Similarly, in the female sample, suicidal ideation was inversely associated with participation in gastric (OR: 0.74, 95% CI: 0.67–0.82), colorectal (OR: 0.71, 95% CI: 0.62–0.81), cervical (OR: 0.75, 95% CI: 0.68–0.84), and breast cancer screening (OR: 0.76, 95% CI: 0.68–0.84). Conclusions: This study suggests that individuals with suicidal ideation demonstrated reduced participation in cancer screening tests. This study highlights the need for targeted support to improve access to cancer screening programs for individuals with mental health problems. Full article

(1) Background: Colorectal cancer is one of the leading causes of cancer-related death, while early detection decreases incidence and mortality. Current screening programs involving fecal immunological testing and colonoscopy commonly bring about unnecessary colonoscopies, which adds burden to healthcare systems. The objective of this study was to provide an assessment of the diagnostic performance of an electronic nose serving as a complementary screening tool to improve current screening programs in clinical settings. (2) Methods: We conducted a case–control study that included patients from a medical center with colorectal cancer and non-colorectal cancer controls. We analyzed the composition of volatile organic compounds in their exhaled breath using the electronic nose. We then used machine learning algorithms to develop predictive models and provided the estimated accuracy and reliability of the breath testing. (3) Results: We enrolled 77 patients, with 40 cases and 37 controls. The area under the curve, Kappa coefficient, sensitivity, and specificity of the selected model were 0.87 (95% CI 0.76–0.95), 0.66 (95% CI 0.49–0.83), 0.81, and 0.85. For subjects at an early stage of disease, the sensitivity and specificity were 0.90 and 0.85. Excluding smokers, the sensitivity and specificity were 0.88 and 0.92. (4) Conclusions: This study highlights the promising potential of breath testing using an electronic nose for enabling early detection and reducing unnecessary treatments. However, more independent data for external validation are required to ensure applicability and generalizability. Full article

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. The risk of disease increases with age, as most CRC patients are over 50 years old. Due to the progressive aging of societies in high-income countries, the problem of CRC will increase. This makes the development of new early detection methods and the implementation of effective screening programs crucial. Key areas of focus include raising population awareness about the importance of screening, educating high-risk populations, and improving and developing early diagnostic methods. The primary goal of this review is to provide a concise overview of recent trends and progress in CRC secondary prevention based on available information from clinical trials. Full article