Search Results (9,504)

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. While established molecular biomarkers such as microsatellite instability (MSI), KRAS, and BRAF are routinely used in clinical practice, the prognostic relevance of tumor suppressor proteins p53 and PTEN remains incompletely defined, particularly when assessed using immunohistochemistry. Objective: The primary aim of this study was to evaluate the prognostic significance of p53 expression and PTEN deficiency in colorectal adenocarcinoma. Secondary aims included assessment of their association with clinicopathological characteristics. Methods: This retrospective cohort study included 103 consecutive patients who underwent surgical resection for colorectal adenocarcinoma. Immunohistochemical analysis of formalin-fixed paraffin-embedded (FFPE) tumor samples was performed to assess aberrant p53 expression and PTEN deficiency. Associations with clinicopathological variables were evaluated, and overall survival was analyzed using Kaplan–Meier curves and Cox proportional hazards regression models. Results: Aberrant p53 expression and PTEN deficiency were both associated with shorter overall survival in univariate analyses. Patients with concurrent aberrant p53 expression and PTEN deficiency demonstrated the poorest survival outcomes. However, in multivariate Cox regression analysis, only nodal status and age remained independent predictors of overall survival, while p53 and PTEN did not retain independent prognostic significance after adjustment for clinicopathological variables. Conclusions: Aberrant p53 expression and PTEN deficiency are associated with reduced overall survival in colorectal cancer; however, their prognostic impact appears secondary to established clinicopathological factors. The combined presence of these alterations may identify a biologically aggressive subgroup of patients with particularly unfavorable outcomes, although this observation should be considered exploratory. Further validation in larger, independent cohorts is required. Full article

Background: Cancer-associated thrombosis is a major cause of morbidity and mortality in oncology patients. Routinely available hematological parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR), may reflect thrombo-inflammatory alterations accompanying thrombotic events in malignancy. Methods: This retrospective exploratory study included 93 patients with solid malignancies who developed radiologically confirmed thrombotic events between 2006 and 2018. Clinical and laboratory data were retrospectively reviewed. Hematological parameters obtained within seven days before and after thrombotic events were compared using appropriate parametric and non-parametric statistical methods. Results: Thrombotic events were most frequently observed in patients with lung, colorectal, breast, and gastric cancers. Gastrointestinal malignancies accounted for 47.3% of cases. Venous thrombotic events represented the majority of cases (63.4%), whereas arterial thrombosis was observed in a smaller subset of patients (10.7%). Pulmonary embolism was identified in 23.7% of patients. Central venous catheter use was significantly associated with subclavian/femoral vein thrombosis (p < 0.001). PLT significantly decreased following thrombotic events (329.3 × 10³/µL vs. 260.8 × 10³/µL, p < 0.001), whereas MPV increased modestly (9.23 ± 1.57 fL vs. 9.40 ± 1.45 fL, p < 0.001). PDW significantly decreased (14.37 ± 2.78 vs. 13.63 ± 3.24, p = 0.011). NLR increased numerically (3.33 ± 2.32 vs. 4.26 ± 4.74) but did not reach statistical significance (p = 0.089). An inverse correlation was observed between PLT and MPV (r = −0.268, p = 0.009). Conclusions: Routinely available hematological parameters, including PLT, MPV, PDW, and NLR, demonstrated measurable alterations in cancer patients with thrombotic events and may reflect thrombo-inflammatory processes associated with malignancy. However, because of the retrospective design, heterogeneous study population, and absence of a non-thrombotic control group, these findings should be considered exploratory and hypothesis-generating rather than evidence of predictive biomarkers. Larger prospective controlled studies are required to clarify their clinical significance. Full article

HCT116 is a colorectal cancer cell line frequently used in anti-tumor drug development experiments as well as in studies of the molecular machinery of eukaryotic cells. It is well characterized by the presence of several single-nucleotide and short mutations in multiple oncogenes and tumor suppressor genes, including KRAS, PIK3CA, MLH1, CTNNB1, CDKN2A, TGFBR2, and BRCA2. However, its landscape of large genomic rearrangements (LGRs) and copy number variants (CNVs) is still far from being fully understood. Therefore, the aim of this study was to identify LGRs and CNVs in several HCT116 cell line samples using Oxford Nanopore sequencing technology, including three samples from the SRA NCBI database, and to compare common and unique variants across all samples. Using the recently developed eLaRodON tool, we identified 22,666 common LGRs, among which more than 70% of tandem duplications and deletions larger than 80 kb were confirmed by CNV analysis. Among LGRs affecting protein-coding sequences, two in-frame rearrangements were identified: a deletion of exons 4–6 and a duplication of exon 10 in the CCSER1 gene, which encodes a cell division regulator protein. Given its high rearrangement rate in various tumors and the clinical significance of its overexpression, this finding may be potentially useful in future research on this cell line. Regarding differences between samples, we found that LGRs in the laboratory sample and in one of the three SRA NCBI samples occurred more frequently via ALR/Alpha repeats than via Alu repeats, in contrast to common LGRs and those unique to the other samples, a finding that may indicate the presence of unique mechanisms of genomic instability. Thus, this study reveals a broad spectrum of large genomic rearrangements and copy number variants that can be identified in the HCT116 cell line using Oxford Nanopore sequencing, including rearrangements specific to distinct cell line samples. Full article

Background: Colorectal cancer (CRC) remains a leading cause of mortality worldwide, with a significant proportion of patients presenting with metastatic disease (mCRC). While molecularly targeted therapies, including anti-EGFR and anti-VEGF agents, have improved survival outcomes, their efficacy is often limited by drug resistance, toxicity, and high costs. There is a growing need for sustainable strategies to enhance therapeutic efficacy. Methods: This review explores the emerging role of plant-derived compounds as synergistic adjuvants. Specifically, PubMed, Scopus, and Web of Science were searched for English-language articles published between January 2004 and June 2026, using combination of terms related to colorectal cancer, metastatic disease, anti-EGFR/anti-VEGF targeted therapy, phytochemicals/natural products, and gut microbiota; both primary studies and reviews were eligible. Results: Targeted therapies such as cetuximab and bevacizumab are the standard of care but face challenges related to RAS/BRAF mutations and primary tumour location. Clinical data demonstrate that while cetuximab improves overall survival in patients with RAS wild-type, left-sided tumours (median OS 31 vs. 26 months; HR 0.76, p = 0.012), progression-free survival remains comparable to that of bevacizumab. Concurrently, natural products like Vitis vinifera, Dendrobium candidum, and quercetin demonstrate significant preclinical potential in inhibiting angiogenesis, inducing apoptosis, and modulating the tumour microenvironment. The gut microbiome, particularly Fusobacterium nucleatum (whose reported prevalence varies widely across cohorts and reaches up to ~98% of CRC tissues only in selected series), has emerged as a key factor in chemoresistance. It should be emphasised that the great majority of the phytochemical-targeted therapy combinations discussed here are currently supported primarily by preclinical (in vitro and animal) studies rather than by clinical trials. Conclusions: Integrating evidence-based phytochemicals with conventional targeted therapies is a mechanistically compelling and potentially sustainable strategy that may enhance therapeutic efficacy, help overcome resistance, and mitigate adverse effects in mCRC management. However, because current support is largely preclinical, these combinations should be regarded as hypothesis-generating and require validation in prospective, biomarker-stratified clinical trials before clinical adoption. Full article

Background/Objectives: We examined whether guidance on dietary habits or nutrition-related problems from healthcare professionals during cancer treatment was associated with quality of life, after treatment. Methods: Cross-sectional data were drawn from the Icelandic Compass study, conducted in 2020–2021 among adults diagnosed with cancer in 2015–2019. The analysis included participants who had completed treatment for breast cancer (n = 341), prostate cancer (n = 137), or colorectal cancer (n = 132), for a total sample of 610 participants. Quality of life (QL) was assessed using the EORTC QLQ-C30 global health status/quality of life scale. Associations were examined using regression models adjusted for age, marital status, education, number of cancer treatments, stage at diagnosis, body mass index, tobacco and alcohol use, and comorbidities. Results: Overall, 26% of participants reported receiving sufficient guidance on general dietary habits during treatment and 19% on nutrition-related problems. On average, three years had passed since diagnosis. Among all participants, guidance on general dietary habits was associated with higher QL scores (β = 5.6; 95% CI: 0.8 to 10.5), as was guidance on nutrition-related problems (β = 5.7; 95% CI: 0.3 to 11.1). In subgroup analyses, statistically significant associations were observed among prostate cancer survivors for both dietary guidance (β = 12.4) and guidance on nutrition-related problems (β = 14.0), and among breast cancer survivors for guidance on nutrition-related problems (β = 8.4). Conclusions: Patient-reported sufficient discussions about dietary habits or nutrition-related problems during treatment were associated with slightly higher post-treatment QL scores. Full article

Background: Predicting long-term outcomes after pulmonary metastasectomy for colorectal cancer remains challenging because existing prognostic methods lack precision. We developed and validated a prognostic scoring system derived from a major international meta-analysis to improve risk stratification and to evaluate the benefit of adjuvant chemotherapy across risk groups. Methods: Using a Japanese registry of 819 patients who underwent lung resection between 2010 and 2019, we constructed a 0–13-point score based on eight variables including tumor size, number, biological markers, and intrathoracic lymph node status, which may require intraoperative or pathological confirmation. Granular data on chemotherapy regimens, timing, and duration were unavailable. Patients were classified as low, intermediate, or high risk. The primary analysis used inverse probability of treatment weighting to adjust for baseline imbalances; however, only 819 of 1657 patients (49.4%) had complete prognostic data, introducing potential selection bias. Results: The score separated patients into three groups with distinct five-year survival rates: 81.1% (low), 67.8% (intermediate), and 59.1% (high). In high-risk patients, chemotherapy was associated with improved overall survival but did not delay recurrence. In low-risk patients, chemotherapy correlated with reduced recurrence-free survival, a finding that persisted after adjustment. Conclusions: This validated scoring system aids individualized surgical decision making by identifying patients unlikely to benefit from routine postoperative chemotherapy. Observed survival advantages in high-risk patients may reflect selection of fitter individuals rather than direct treatment effects, underscoring the need to address selection bias in future trials. Full article

To evaluate the diagnostic performance and clinicopathologic relevance of a multi-locus circulating tumor DNA methylation assay. In this prospective, single-center, case-control exploratory study, we enrolled 35 patients with colorectal cancer undergoing surgery and 57 healthy controls undergoing screening colonoscopy at the Asan Medical Center, Seoul, Republic of Korea between July 2024 and January 2025. Peripheral blood was collected before surgery or colonoscopy, and circulating tumor DNA methylation was analyzed using a multi-locus panel targeting Septin9, IKZF1, BCAT1, Septin9-2, BCAN, and VAV3. The main outcomes were test accuracy (sensitivity, specificity, and area under the curve [AUC]) and associations between methylation marker positivity and clinicopathologic features. Circulating tumor DNA was positive in 74.3% of the patients and 12.3% of controls, yielding a sensitivity of 74.3%, specificity of 87.7%, and an AUC of 0.837, whereas serum carcinoembryonic antigen exhibited lower sensitivity (25.7%). Sensitivity in stage I disease was limited (36.4%). Circulating tumor DNA-positive tumors were larger (5.7 cm vs. 2.2 cm, p < 0.001) and had more advanced T and N stages. The number of positive markers increased with pathologic stage (p = 0.003). Individual marker analysis revealed that BCAT1, Septin9-2, and VAV3 were associated with higher T stage, whereas BCAN positivity was linked to nodal metastasis. The six-marker circulating tumor DNA methylation assay demonstrated acceptable diagnostic accuracy, with multi-locus patterns associated with tumor burden and invasive features. However, sensitivity for early-stage disease was limited. The assay may serve as a complementary tool for screening and risk stratification. Full article

Background/Objectives: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in treatment, outcomes for advanced CRC remain unsatisfactory due to uncontrolled proliferation, metastasis, and recurrence. This study investigated the anti-cancer effects of KMU-11342, an indolin-2-one-based multi-protein kinase inhibitor with previously reported anti-inflammatory properties, in human colorectal cancer models. Methods: The anti-cancer effects of KMU-11342 were evaluated in colorectal cancer cells and further investigated in three-dimensional (3D) spheroid and patient-derived organoid models. Cell proliferation, migration, apoptosis, and cell cycle progression were assessed. Kinase activity profiling and molecular docking analyses were performed to identify potential targets and characterize the underlying signaling pathways. Results: KMU-11342 significantly inhibited the proliferation and migration of CRC cells. It reduced CRC cell density by 58.9% and 83.3% at 0.5 and 1 μM, respectively. These effects were accompanied by G2/M cell cycle arrest and apoptotic cell death. In 3D models, spheroid formation was markedly reduced and stemness-related characteristics were diminished. Patient-derived CRC organoids also showed decreased viability, exhibiting 38.6% and 77.4% reductions at 1 and 2 μM, respectively. These effects were observed in a dose-dependent manner in both two-dimensional (2D) and 3D colorectal cancer models. Kinase activity profiling and molecular docking analyses identified glycogen synthase kinase 3 beta (GSK3β) and cyclin-dependent kinase 1 (CDK1) as potential mediators of the anti-cancer effects of KMU-11342 through the p53/nuclear factor kappa B (NF-κB) and FoxO1 signaling axes, respectively. Conclusions: KMU-11342 exhibits potent anti-tumor activity against CRC through suppressing proliferation, migration, and stemness in both 2D and 3D models, including patient-derived organoids. Its effects may be mediated, at least in part, through modulation of GSK3β and CDK1 via the p53/NF-κB and FoxO1 signaling pathways. Full article

Obesity is increasingly recognized as a complex systemic disorder rather than a simple consequence of excess energy intake and fat accumulation. This review presents a systems biology framework that examines how obesity-driven disruption of inter-organ communication networks contributes to chronic disease susceptibility, with particular emphasis on colorectal cancer (CRC). Disrupted signaling among the brain, adipose tissue, liver, skeletal muscle, gut, and immune system generates maladaptive feedback loops that promote chronic metabolic inflammation (metaflammation), loss of physiological resilience, and progressive metabolic dysfunction. Within this framework, obesity is redefined as a network disease characterized by neuroendocrine dysregulation, adipose tissue remodeling, immune dysfunction, impaired organ crosstalk, and alterations in the gut microbiome. A central feature of this dysregulation is persistent low-grade inflammation driven by immune-metabolic reprogramming and sustained activation of inflammatory pathways. Obesity-associated metaflammation is further linked to accelerated biological aging through mechanisms involving cellular senescence, mitochondrial dysfunction, oxidative stress, and impaired metabolic resilience. These interconnected processes create a tumor-promoting environment by enhancing oncogenic signaling, disrupting intestinal barrier integrity, altering microbial and metabolic signaling, impairing immune surveillance, and promoting epithelial dysfunction, thereby increasing susceptibility to CRC. The review also examines how behavioral, circadian, environmental, and socioeconomic factors influence metabolic health and cancer risk. Finally, emerging translational opportunities, including biomarker-guided risk stratification, precision prevention, metabolic network restoration, and integrative lifestyle and pharmacological interventions, are discussed. Collectively, this review reframes obesity as a whole-body regulatory disorder and provides an integrated conceptual framework linking metabolism, inflammation, aging, and colorectal carcinogenesis to inform future prevention and therapeutic strategies. Full article

Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed DNA, histones, and proteins released by activated neutrophils. Originally identified as an innate defense mechanism against pathogens, NETs have since been implicated in cancer progression and immune evasion. Within the tumor microenvironment (TME), NETs suppress anti-tumor immunity through multiple mechanisms, including the physical exclusion of CD8⁺ cytotoxic T lymphocytes from the tumor interior and upregulation of exhaustion markers via checkpoint ligands. This review synthesizes current preclinical and clinical evidence on the interplay between NETs and CD8⁺ T cells across multiple malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, cholangiocarcinoma, colorectal cancer, bladder cancer, hepatocellular carcinoma, skin cancer, and penile cancer. Cancer-specific mechanisms of NET-mediated immune suppression are discussed, including IL-8, IL-17, CXCL6, and TGF-β-driven NETosis pathways. Clinical data consistently demonstrate that elevated NET levels correlate with reduced CD8⁺ T cell infiltration, T cell dysfunction, and worse patient outcomes. Emerging therapeutic strategies targeting this axis are reviewed, including DNase I-mediated NET degradation, Peptidyl arginine deiminase 4 (PAD4) inhibition, CXCR2 blockade, and combination approaches with immune checkpoint inhibitors. These interventions have shown promise in restoring CD8⁺ T cell cytotoxicity and overcoming immunotherapy resistance in preclinical models. Collectively, the evidence supports the NET-CD8⁺ T cell axis as a promising prognostic and therapeutic target warranting further clinical investigation. Full article

Background: Apoptosis is a fundamental process for maintaining tissue homeostasis, and its dysregulation is closely linked to the development of numerous diseases, including colorectal cancer. In recent years, dietary polyphenols have gained interest due to their antioxidant, pro-apoptotic, and chemopreventive properties. Artichoke (Cynara scolymus L.) by-products are rich source of hydroxycinnamic acids and flavonoids, making them promising source of bioactive compounds. Methods: In this study we evaluated the cytotoxic and pro-apoptotic activity of four aqueous extracts obtained from artichoke bract by-products, including one commercial hybrid (CAPB) and three local Apulian varieties (BriB, VaMB, LMTB), in human colorectal adenocarcinoma cell lines (Caco-2 and HT29). The extracts were characterized according to their total polyphenol content and phenolic profile. Results: The selected artichoke by-product extracts exhibited significant cytotoxic effects both in a concentration- and time-dependent manner, with concentrations ≥ 2 mg/mL significantly reducing cell viability and nearly abolishing it at 4 mg/mL after 48 h. Moreover, treatment with the extracts modulated the expression of apoptosis-related proteins, characterized by an increase in pro-apoptotic markers (Bax, caspase-9, caspase-3) and a decrease in the anti-apoptotic protein Bcl-2, suggesting activation of the mitochondrial apoptotic pathway. In particular, the BriB extract was able to induce an apoptosis rate higher than 80% in Caco-2 cells and achieved comparable rates in HT29 cells at concentrations of 2–3 mg/mL. Conclusions: Overall, these findings demonstrate that artichoke by-product extracts exert significant pro-apoptotic effects in colorectal cancer cells and highlight their potential as sustainable sources of bioactive compounds for nutraceutical or adjuvant anticancer applications. Full article

Background/Objectives: Pulses are nutrient-dense, low-glycaemic legumes rich in fibre and bioactive compounds that may modulate carcinogenesis through effects on diet quality, metabolism, and the gut microbiome. This scoping review mapped human evidence on pulses in relation to cancer risk reduction and related mechanistic and survivorship-relevant outcomes. Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Joanna Briggs Institute (JBI) Population, Concept and Context (PCC) guidance, we searched CENTRAL, Scopus and PubMed (2014–31 December 2025), supplemented by backward and forward citation tracking, for English-language human studies in which pulses were a defined exposure or intervention and cancer-specific clinical outcomes or biomarkers were reported. Exposures are described using the original ‘legume’ terminology, with pulse-specific interpretation restricted to FAO-defined pulses or clearly dry pulse forms and to pulse-dominant legume intake where the constituent items were predominantly pulses but preparation was not specified. Results: After screening 1244 records, 15 studies met the inclusion criteria, comprising five case–control studies, five 4-week randomised controlled trials (RCTs), one 8-week randomised crossover trial, one controlled feeding study, two prospective cohort studies, and one other prospective study. Observational data from a single pooled case–control study suggest that higher pulse-dominant legume intake is compatible with modestly lower colorectal cancer risk, although the findings are mixed and often attenuate after adjustment for lifestyle and dietary confounders. Evidence for breast and oesophageal cancer and all-cancer mortality is limited, frequently subgroup-specific or highly sensitive to confounder control, and survivorship endpoints are represented mainly by short-term mechanistic and feasibility trials in colorectal cancer survivors rather than by long-term clinical outcomes. Notably, five of these navy bean interventions were conducted by a single research group using similar protocols, which constrains the independence of replication. Conclusions: Pulses can be considered practical components of cancer-protective dietary patterns, especially for colorectal cancer, but the heterogeneity of study designs, short-term interventions, limited sample sizes, and lack of preparation-specific exposure data preclude firm causal inferences; longer-term, rigorously designed trials and detailed observational work are needed to refine pulse-based recommendations for cancer risk reduction and to clarify any role in survivorship care. Full article

Background/Objectives: The double-strand break repair protein MRE11 forms the core of the MRE11/RAD50/NBS1 (MRN) complex. Cancers with reduced MRE11 expression have been suggested to be more sensitive to radio-chemotherapy and may be subject to synthetic lethality. The aim of this study was to assess the prevalence of MRE11 deficiency and the potential role and clinical significance of elevated and/or reduced MRE11 expression in human cancer. Methods: A tissue microarray containing 14,966 samples from 134 different tumor entities was analyzed for MRE11 by immunohistochemistry. Results: In normal tissues, strong nuclear MRE11 staining occurred in almost all cell types. In cancers, nuclear MRE11 staining was strong in 11,797 (91.0%), moderate in 1018 (7.9%), weak in 86 (0.7%), and completely absent (MRE11 deficiency) in 55 (0.4%) of 12,956 informative tumor samples. Only six tumor entities had more than one MRE11-deficient cases including hepatocellular carcinoma (9 of 193), intestinal type gastric adenocarcinoma (4 of 208), endometrioid endometrial carcinoma (5 of 268), pulmonary adenocarcinoma (2 of 165), colorectal adenocarcinoma (CRC, 16 of 2183), and clear cell renal cell carcinoma (ccRCC, 7 of 1011). Reduced MRE11 staining was associated with mismatch repair deficiency (dMMR) in CRC and in gastric adenocarcinoma (p < 0.0001 each), advanced pT stage (p = 0.0003) and L1 status (p = 0.0019) in testicular seminoma, high grade (p < 0.05), advanced pT (p < 0.0001), and high UICC stage (p = 0.0014) in ccRCC, advanced pT stage in high-grade serous ovarian carcinoma (p = 0.0396), and nodal metastases in papillary thyroid cancer (p = 0.0332). Conclusions: MRE11 is highly expressed in most cancers. Reduced MRE11 expression is associated with aggressive phenotype in multiple cancer types. The potential to exploit MRE11 deficiency as a target for synthetic lethality deserves to be further explored. Full article

Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with poor survival rates of late-stage disease. While immune checkpoint blockade (ICB) therapy has transformed treatment for mismatch repair-deficient (MMRd)/microsatellite instability-high (MSI-H) tumors, most CRC cases are mismatch repair-proficient (MMRp)/microsatellite-stable (MSS) and derive little to no benefit from current immunotherapy regimens. Tumor-associated macrophages (TAMs) constitute a significant component of the tumor microenvironment (TME) and exhibit a phenotypic gradient between pro-inflammatory (M1-like) and anti-inflammatory, immunosuppressive (M2-like) states. Although their polarization status is increasingly recognized as a key modulator of immunotherapy efficacy in CRC, a comprehensive synthesis of the literature regarding macrophage polarization and its relevance to improving CRC immunotherapy remains lacking. Methods: A systematic literature search was conducted across PubMed, EMBASE, and ScienceDirect from inception to December 2025 using terms encompassing macrophages, immunotherapy, immune checkpoint expression, colorectal cancer, and microsatellite stability status. Title, abstract, and full-text screening were performed independently by multiple authors. Sixty-five studies were included following PRISMA guidelines. The protocol was prospectively registered on PROSPERO (ID: CRD420251244320). Results: Three key themes were identified: (1) macrophage-mediated mechanisms of resistance to ICB, including M2 polarization driven by the PI3Kγ, STAT3, mTOR, and SIRT-1 axes, immunosuppressive cytokine production (IL-10, TGF-β), and altered immune checkpoint ligand expression; (2) macrophage polarization status and associated biomarkers as prognostic indicators of therapeutic response; (3) emerging macrophage-targeted therapeutic strategies in ongoing clinical trials, including CSF1R inhibitors, CD40 agonists, CD47/SIRPα blockade, and STING agonists. Conclusions: TAM polarization is a critical determinant of immunotherapy resistance and patient prognosis in CRC. Macrophage-targeted strategies, particularly M2-to-M1 repolarization approaches used in combination with existing ICB regimens, represent a promising avenue for expanding immunotherapy efficacy beyond MSI-H disease. Further translational research and randomized controlled trials are needed to validate these targets clinically. Full article

Background: Colorectal cancer (CRC) prognosis, particularly in liver metastasis (CRLM), is influenced by histopathological and molecular factors. Methods: A narrative analysis of the specialized literature was conducted using databases such as PubMed, MEDLINE, Scopus, and Embase. The review focused on original articles published between 2005 and 2025. Results: Lymph node involvement is a critical prognostic factor, with lymph node-positive CRC correlating with increased risk of liver metastasis and significantly reduced survival rates. Poorly differentiated tumors (G3) exhibit a higher likelihood of metastasis, including liver involvement, and are associated with worse clinical outcomes. Vascular emboli and perineural invasion are indicative of hematogenous spread and higher metastatic potential, leading to poorer survival outcomes. Genetic mutations, such as KRAS, NRAS, and BRAF, are associated with therapy resistance, complicating treatment and highlighting the importance of personalized approaches. MSI-H and HER2 amplification further affect treatment response, with MSI-H tumors showing a favorable response to immunotherapy, while HER2-positive CRCs may benefit from targeted therapies. Tumor budding, high levels of which predict poor survival, is another key histopathological feature associated with aggressive metastatic behavior. Systemic inflammatory markers, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and C-Reactive Protein-to-Albumin Ratio (CAR), offer prognostic insights into CRLM patient survival. Conclusions: Histopathological features, molecular alterations, and immune microenvironment factors significantly impact the prognosis of CRC with liver metastasis. The integration of molecular profiling, immunotherapy, and targeted therapies offers promise for improving treatment outcomes. Personalized treatment strategies, incorporating these factors, are essential for overcoming therapy resistance and improving survival in CRLM patients. Full article