Treatment Of Colorectal Cancer Research Articles

Prognostic and therapeutic value of a 23-gene risk score tailored to the molecular characteristics of mucinous colorectal cancer.

Mucinous adenocarcinoma (MuC), a colorectal cancer (CRC) subtype, exhibits distinct molecular features and poorer response to chemoradiotherapy than non-mucinous adenocarcinoma (NMuC). Conventional treatments often fail to address CRC heterogeneity, particularly in stage II disease. Therefore, improved biomarkers for risk stratification and personalised treatment are needed. We analysed gene expression and mutation data from 259 CRC samples to identify characteristics of MuC. A 23-gene risk score (MuC-RS) was developed and validated across four independent cohorts (n = 1157). Statistical analyses, including generalised linear model likelihood ratio tests, Kaplan-Meier curves, log-rank tests, and Cox regression models, evaluated the prognostic utility of the MuC-RS. MuC showed significant upregulation of fibroblast-associated genes, pathways related to epithelial-mesenchymal transition, and mucin glycosylation. The MuC-RS effectively stratified patients into high-risk (MuC-H) and low-risk (MuC-L) groups, with multivariate analysis confirming its prognostic value (HR = 1.72, 95% CI = 1.31-2.25, P < 0.001). Stage II MuC-L patients had poorer outcomes after conventional chemotherapy, but responded better to immune checkpoint inhibitors (ICIs), linked to higher tumour mutation burden and immune activation. The MuC-RS effectively predicts recurrence and guides personalised treatment in CRC, particularly benefiting stage II MuC patients through improved risk stratification and treatment selection.

Pyrvinium Pamoate and BCL-XL Inhibitors Act Synergistically to Kill Patient-Derived Colorectal Adenoma Organoids

Current systemic therapies for advanced colorectal cancer (CRC) have limited efficacy, so more effective strategies for the treatment and prevention of CRC are needed. The majority of colorectal cancers are initiated by mutations in Wnt signalling pathway genes, including mutations in the APC gene, which result in a truncated APC protein and lead to excess signalling from β-catenin and the formation of pre-cancerous adenomas. The aim of this study was to determine if targeting the Wnt pathway in combination with pro-apoptotic mimetics altered the proliferative capacity or viability of human colorectal adenoma cells. Patient-derived colorectal adenoma organoid cultures were established from colon adenoma tissue collected by colonoscopy and recapitulated the histopathology of primary colorectal adenoma tissue. The growth of colorectal adenoma organoids is inhibited by the Wnt-signalling antagonist pyrvinium pamoate (PP) and a pro-apoptotic inhibitor of BCL-XL but not BCL-2 (venetoclax) or MCL-1 inhibitors. At low concentrations, the PP and the BCL-XL inhibitor combination demonstrated potent synergy and induced apoptosis in APC-defective patient-derived adenoma organoids, even in the presence of oncogenic KRAS or BRAF mutations, providing a new strategy for colon cancer prevention.

Sophocarpine suppresses MAPK-mediated inflammation by restoring gut microbiota in colorectal cancer.

Sophocarpine suppresses MAPK-mediated inflammation by restoring gut microbiota in colorectal cancer.

Influence of Citrobacter freundii on NINJ2 Expression and Oxaliplatin Resistance in Colorectal Cancer.

Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, is widely used in the treatment of colorectal cancer (CRC). However, some patients do not respond effectively to oxaliplatin, and intrinsic resistance to the drug poses a significant challenge. Recent studies have revealed an association between the gut microbiome and the progression of CRC. We hypothesized that Citrobacter freundii, a component of the gut microbiome, contributes to oxaliplatin resistance by regulating specific gene expression in CRC cells. A bacterial culture filtrate from Citrobacter freundii was employed in the experiments. The CRC cell line RKO, following exposure to this filtrate, was analyzed using high-throughput RNA sequencing. Candidate genes were identified through MTT assays, siRNA knockdown, and overexpression experiments. Apoptosis and reactive oxygen species (ROS) assays were performed to investigate the underlying mechanisms. Finally, a xenograft mouse model was used to evaluate oxaliplatin resistance in vivo. Exposure to bacterial culture filtrate from Citrobacter freundii induced oxaliplatin resistance in RKO cells with downregulation of the NINJ2 gene as a possible molecular mechanism. ReducedNINJ2 gene expression suppressed oxaliplatin-induced apoptosis and ROS generation. A tendency toward reduced oxaliplatin efficacy was observed in vivo when NINJ2 gene expression was suppressed. This study demonstrates that Citrobacter freundii promotes oxaliplatin resistance in CRC through downregulation of NINJ2 gene. NINJ2 gene may serve as a predictive biomarker and therapeutic target to overcome oxaliplatin resistance in CRC.

Antitumor Effects of Epigallocatechin-3-Gallate on Colorectal Cancer: An In Vitro and In Vivo Study.

Tea consumption is widely reported to have beneficial effects on cancer prevention. Epigallocatechin-3-gallate (EGCG), a major bioactive component of green tea, has demonstrated anti-proliferative effects against various cancer cell types. This study aimed to evaluate the antitumor effects of EGCG on human colon and colorectal cancer cells both in vitro and in vivo and to identify microRNAs (miRNAs) associated with its antitumor activity. We investigated the ability of EGCG to inhibit cell proliferation by apoptosis and analyzed its effects on cell cycle-related molecules in multiple human colon cancer cell lines. Additionally, EGCG-induced alterations in activated receptor tyrosine kinases and angiogenesis-related proteins were assessed using protein arrays. miRNA array analysis was performed to identify EGCG-regulated miRNAs. An in vivo mouse xenograft model was used to assess the tumor-suppressive potential of EGCG. EGCG induced apoptosis and significantly suppressed the proliferation of colon cancer cells, both in vitro and in vivo. In the miRNA array analysis, EGCG-treated CW-2 cells exhibited up-regulation of seven miRNAs and down-regulation of eight miRNAs. Notably, the down-regulation of hsa-miR-187-5p was most significant. EGCG suppresses the proliferation of human colon cancer cells through induction of apoptosis. Down-regulation of hsa-miR-187-5p may be a potential marker for the effect of EGCG in regulating colorectal cancer. These findings suggest that EGCG may serve as a promising therapeutic agent or adjunct in the treatment of colorectal cancer.

Bioactive components of Jiedu Sangen decoction against colorectal cancer: A novel and comprehensive research strategy for natural drug development.

Bioactive components of Jiedu Sangen decoction against colorectal cancer: A novel and comprehensive research strategy for natural drug development.

CRISPR/Cas9-directed epigenetic editing in colorectal cancer.

CRISPR/Cas9-directed epigenetic editing in colorectal cancer.

Computer-aided unveiling molecular mechanisms of Xylocarpus granatum against colorectal cancer: therapeutic intervention targeting P13K-AKT signaling pathway.

Computer-aided unveiling molecular mechanisms of Xylocarpus granatum against colorectal cancer: therapeutic intervention targeting P13K-AKT signaling pathway.

Innovative horizons: harnessing drug repositioning for targeted therapeutics in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new treatment options are urgently needed. Drug repositioning has gained attention as a strategy to identify new therapeutic applications for CRC. This approach can expedite drug development and reduce costs by leveraging drugs already undergoing safety testing. Computational and experimental methods are used to identify potential candidates for drug repositioning in CRC. However, challenges such as a lack of comprehensive knowledge regarding the molecular mechanisms underlying the disease and resolving intellectual property and regulatory issues must be overcome. Drug repositioning has the potential to revolutionize CRC treatment by identifying new drugs for gastrointestinal tumors. For example, metformin, a biguanide antidiabetic drug, is effective for CRC by inhibiting the PI3K-Akt-mTOR pathway. COX-2 inhibitors, which block cyclooxygenase-2 to reduce inflammation and cancer progression, may also be examples of drug repositioning for CRC. Several approaches have been employed to identify potential candidates for drug repositioning in colorectal cancer, including computational methods such as data mining and network analysis and experimental techniques such as high-throughput screening and in vitro assays. Despite its potential benefits, drug repositioning in colorectal cancer faces several challenges, including the lack of comprehensive knowledge regarding the disease's molecular mechanisms. Further research is needed to overcome these challenges and identify specific drug targets for CRC treatment. With continued efforts and advancements in this field, drug repositioning has the potential to revolutionize colorectal cancer treatment. This review provides an overview of drug repositioning in the context of colorectal cancer, highlighting its advantages, challenges, and potential future directions.

Can Pembrolizumab or Nivolumab be efficiently used against colorectal cancers with defective mismatch repair and high index of microsatellite instability?

Patients with metastatic colorectal cancer (CRC) presenting defective mismatch repair (dMMR) and/or high index of microsatellite instability (MSI-H) are suitable candidates for immunotherapy with immune checkpoint inhibitors (ICIs), such as pembrolizumab and nivolumab. However, the use of these ICIs as neoadjuvant treatment for non-metastatic and metastatic CRCs with these specific molecular alterations is still controversial. Thus, this systematic review (PROSPERO CRD42021258676) evaluated the benefits, toxicity profile, and clinical outcomes of pembrolizumab and nivolumab as neoadjuvant therapy for CRC with dMMR and/or MSI-H. For this, MEDLINE, Scopus, Cochrane Library, and Science Direct databases were used. Twenty-five case reports and four randomized clinical trials were included, and the main outcomes analyzed were overall survival, progression-free survival, pathological response through RECIST 1.1, and the Eastern Cooperative Oncology Group (ECOG) performance status, respectively. In general, the evaluated studies were well conducted according to the assessment tools, and the evidence suggests that combinations of nivolumab plus ipilimumab were more effective to treat metastatic CRC with dMMR and/or MSI-H than nivolumab alone. Regarding pembrolizumab, clinical evidence demonstrated its safety and efficiency for patients with this subtype of CRC in metastatic and locally advanced stages. This review indicates therapeutic promising potential of ICIs for patients with dMMR and/or MSI-H CRCs. Additionally, alterations in PI3K and JAK pathways are important mechanisms of resistance and represent an opportunity for the development of new drugs. Therefore, molecular investigations should be performed to uncover causes of therapeutic failure.

Dendritic cell membrane-based DCsLipo@MnO2@siCTLA4@PD-1α nanomedicine for the treatment of Lynch syndrome-related colorectal cancer

Dendritic cell membrane-based DCsLipo@MnO2@siCTLA4@PD-1α nanomedicine for the treatment of Lynch syndrome-related colorectal cancer

Circulating tumor DNA: A new tool to predict recurrence and guide treatment of colorectal cancer.

Circulating tumor DNA: A new tool to predict recurrence and guide treatment of colorectal cancer.

Phyllanthus Niruri as a Natural Therapeutic Agent for Colorectal Cancer: A Literature Review

Background: Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide, with increasing incidence and mortality rates. Conventional treatments such as chemotherapy and radiation therapy often have limited efficacy and significant side effects, prompting the search for alternative therapies. Phyllanthus niruri (PNL), a traditional medicinal plant, has shown promising anticancer properties in various studies. This systematic review aims to evaluate the relationship between Phyllanthus niruri and colorectal cancer by analyzing existing literature, including in vitro, in vivo, and clinical studies. The review highlights the mechanisms of action, efficacy, and potential of PNL as an adjunct or alternative treatment for colorectal cancer. A comparison of findings from various international journals is provided to assess the consistency and reliability of the results.

The gut-brain axis in the context of colorectal cancer.

The gut-brain axis in the context of colorectal cancer.

Epigenetically targeting PRMT5 promotes antitumor immunity by inducing endogenous retroviruses expression and triggering viral mimicry response.

Epigenetically targeting PRMT5 promotes antitumor immunity by inducing endogenous retroviruses expression and triggering viral mimicry response.

METTL14-mediated m6A modification of ETV4 inhibits tumor development in colorectal cancer.

METTL14-mediated m6A modification of ETV4 inhibits tumor development in colorectal cancer.

ETV4 promotes the growth, metastasis, glycolysis, and oxaliplatin resistance of colorectal cancer by transcription activation-mediated SLC38A5 upregulation.

ETV4 promotes the growth, metastasis, glycolysis, and oxaliplatin resistance of colorectal cancer by transcription activation-mediated SLC38A5 upregulation.

Chronopharmacokinetic model analysis of 5-fluorouracil following S-1 administration in rats: comparison with infusion and other prodrugs for chronochemotherapy.

Chronopharmacokinetic model analysis of 5-fluorouracil following S-1 administration in rats: comparison with infusion and other prodrugs for chronochemotherapy.

Food-derived bioactive peptides as emerging therapeutic agents: Unlocking novel strategies for colorectal cancer treatment.

Food-derived bioactive peptides as emerging therapeutic agents: Unlocking novel strategies for colorectal cancer treatment.

OTOP3 functions as an oncogenic regulator of ferroptosis-mediated colorectal cancer progression.

OTOP3, a proton channel located at 17q25.1, drives colorectal cancer growth by enhancing c-Myc stability and inhibiting ferroptosis through GPX4 regulation. Inhibition of OTOP3 suppresses CRC proliferation via c-Myc destabilization, ROS accumulation, and lipid peroxidation, while modulating metabolic shifts linked to the Warburg effect. These findings position OTOP3 as a novel therapeutic target for CRC by disrupting oncogenic signaling and ferroptosis resistance. To investigate OTOP3's role in CRC growth/metastasis and its link to ferroptosis and metabolic reprogramming. To evaluate OTOP3 targeting as a therapeutic strategy. Colorectal cancer (CRC) cell lines were transfected with OTOP3 siRNA to suppress gene expression, followed by cell viability assays to assess proliferation changes. Western blotting quantified c-Myc and GPX4 levels, while fluorescent probes measured ROS accumulation and lipid peroxidation. Ferroptosis induction was validated using ferroptosis inhibitors, and glycolytic activity was analyzed via glycolysis-related gene expression and lactate production assays. OTOP3 inhibition destabilized c-Myc, suppressed proliferation, and induced ferroptosis via GPX4 reduction, ROS accumulation, and lipid peroxidation. Altered glycolysis factors indicated enhanced Warburg effect. Our study provides compelling evidence that targeting OTOP3 effectively suppresses colorectal cancer proliferation by reducing c-Myc protein stability and inducing ferroptosis. These effects are closely associated with metabolic shifts characteristic of the Warburg effect, emphasizing OTOP3 as a potential therapeutic target in colorectal cancer treatment.