Colon Cancer

The succinimides antiproliferative effect on A549 cell line given as IC50 was statistically significant associated with their molar refractivity (p = 0.033), and lipophilicity (XlogP3, p = 0.043), respectively. Finally, the most promising drug candidate with the most pronounced anticancer activity was compound D11 against lung carcinoma (A549) cell lines with an IC50 comparable to doxorubicin.

P=N/A, N=257, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=110, Active, not recruiting, Compugen Ltd | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

In the present study, the CTNP/B.b-sup was demonstrated to possess the capability of modulating genes associated with CRC progression, thereby highlighting its significant pro-apoptotic potential. It can be concluded that CTNP/B.b-sup is a suitable drug delivery system with anticancer properties, which can be regarded as a complementary therapeutic approach for the treatment of CRC.

Our findings suggest that CDX1/2 cooperatively suppressed colonic tumorigenesis and cancer stemness by antagonizing β-catenin via the DSIF and PAF1 complexes. Additionally, DSIF and PAF1 complexes acted as transcriptional platforms that integrated and funneled both tumor-suppressive and oncogenic signals into the expression of genes that control colon cancer stemness.

Lusichelin B (2) exhibited cytotoxicity against colon carcinoma cells while reversing multidrug resistance via ABCB1 efflux pump modulation. These findings expand our understanding of cyanobacterial metallophores in microbial metal homeostasis and highlight their biological potential.

The absence of GPR4 significantly attenuated tumor progression in the colon of mice, and this result correlated with increased cytotoxic cell activity and reduced presence of tumor-associated macrophages and neutrophils. GPR4 represents a potential new target for therapeutic intervention.

P4, N=200, Recruiting, Assaf-Harofeh Medical Center | Trial primary completion date: Apr 2025 --> Sep 2025

Most compounds exhibited greater anti-proliferative activity compared to the positive control MK2206, while also demonstrating lower cytotoxicity against normal cells than shikonin...A 3D-QSAR model was constructed to understand the relationship between the structure of the shikonin derivatives and their anti-proliferative activity. The in silico ADMET and toxicity prediction studies revealed a few undesired pharmacokinetic attributes of our compounds.

P2, N=107, Completed, Zhejiang University | Not yet recruiting --> Completed | Trial completion date: Dec 2025 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

Nomoscore-high patients exhibited resistance to AMG.706 and ABT.888, suggesting therapeutic vulnerabilities. These findings highlight SUMOylation plays a critical role in CRC heterogeneity, immune modulation, and prognosis, offering a novel biomarker system for risk stratification and personalized therapy.

P=N/A, N=156, Completed, Sun Yat-sen University

P=N/A, N=370, Recruiting, Hospital Universitari de Bellvitge | Trial completion date: Dec 2024 --> Jan 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

Breast cancer and colon cancer can precede gynaecologic cancer. Individualization of somatic and genetic testing in colorectal and breast cancers will allow screening and prevention of second gynaecologic malignancies.

P=N/A, N=83663, Recruiting, Washington University School of Medicine | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026

We developed a novel DCRI that accurately predicts COAD prognosis and immunotherapy response. PPP2CB was identified as a potential therapeutic target, offering new insights for personalized COAD treatment strategies.

Additionally, in an azoxymethane-induced colorectal carcinogenesis model, Bach1-/- mice exhibited a significant increase in aberrant crypt foci formation. These findings suggest that Bach1 deficiency contributes to colorectal tumorigenesis by promoting epithelial hyperproliferation.

P2/3, N=62, Terminated, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | N=439 --> 62 | Recruiting --> Terminated; Adjustment of the Company's R&D Strategy

In vitro experiment, KCNC3 knockdown inhibited the growth and metastasis of SW1116 cells. This study demonstrated that the high expression of KCNC3 contributes to the growth and invasion of CRC and confers with immunosuppressive microenvironment that can promote tumor progression and can be used to predict the poor clinical outcome of CRC patients.

Conversely, L. casei 393 ingestions, starting at the same time as CAC induction, restored colon architecture and modulated cytokine levels and gene expression. The present experimental work supports the therapeutic potential of L. casei 393 against CAC, as it shows that its ingestion restored the damaging effect of AOM-DSS through its anti-inflammatory properties that helped modulate KRAS and APC mRNA expression.

Further, LIAS emerged as a potential therapeutic target. Our findings may provide new avenues for targeted cancer treatment in READ.

A murine model was used to assess the immunomodulatory effects of folinic acid, oxaliplatin, and 5-fluorouracil (FOLFOX) chemotherapy on TLS formation. Their spatial distribution carries distinct prognostic implications, and FOLFOX-induced TLS formation suggests a dual role in cytotoxicity and immune activation. Incorporating TLS assessment into clinical workflows may improve risk stratification and guide personalized treatment, especially in designing immunochemotherapy strategies.

This review introduces the involvement of COX-2 in cancer via different pathways and provides a comprehensive review of the most recent updates on COX-2 inhibitors as potential anticancer candidates. This review aims to spark fresh thinking in the pursuit of more logical COX-2 inhibitor designs that may effectively treat cancer.

Subgroup analyses underscore the potential advantages of adjuvant chemotherapy in high-risk groups of both cohorts and the low-risk group of the right-sided cohort. These findings may inform the optimization of therapeutic strategies for EOCC patients.

Our in vitro data were further supported by molecular docking, which showed a higher binding energy of the proteins (Bax, Bcl-2, and p53) with Cur + PL. Overall, our findings highlight the potent synergistic effects of the Cur and PL combination, which can be exploited as a combination therapy for CRC.

The postoperative CRP response was not significantly associated with improved long-term survival outcomes in patients undergoing RAS or LAS for UICC stage I-III colon cancer.

Kinetic studies, represented by Lineweaver-Burk double-reciprocal plots, revealed that compounds 4b and 6e as well as quercetin are mainly behaved as competitive inhibitors of the PIM-1 kinase enzyme. Conversely, compounds 6a and 6i exhibit both competitive and non-competitive inhibition of PIM-1 kinase enzyme.

In contrast, 10 mM butyrate promotes macrophage cell death, does not inhibit LPS-induced production of TNF-α, and promotes production of IL-1β, while production of anti-inflammatory IL-10 is reduced in a mechanism involving G protein-coupled receptors, the lipid transporter CD36, and the kinase SRC. We propose that butyrate is a signaling molecule for intestinal integrity, since intestinal disruption exposes macrophages to high butyrate concentrations.

MLCK inhibition disrupts myosin II activity, leading to unresolved replication stress, DNA damage, and activation of the p53-mediated apoptosis pathway. Our findings suggest that targeting MLCK offers a promising therapeutic strategy for MYC-driven cancers.

Activation of PXR also mitigates intestinal inflammation by antagonizing the NF-κB signaling, while CAR activation affects bile acid metabolism and T-cell homeostasis. These findings underscore the complex and context-dependent roles of PXR and CAR in the intestinal tracts, offering potential therapeutic targets for gastrointestinal diseases.

The combination of VEGFA siRNA and NAMPT siRNA more effectively inhibited cell growth. Anti-CHI3L1 antibody inhibited the production of ATP and NADH in colon cancer and had a higher inhibitory effect on these levels when combined with NAMPT siRNA These data demonstrated that anti-CHI3L1 antibody is useful as a potential therapy for colon cancer by inhibiting NAMPT-dependent VEGFA expression and ATP and NADH levels.

The expression levels of LRP2 were intimately correlated with gene mutations, prognosis, pathological stage and the sensitivity to anticancer drugs in COAD. Augmented levels of LRP2 would manifest poor prognosis, which furnished novel insights for clinical diagnosis and treatment in COAD. LRP2 could extensively facilitate the proliferation ability of colon cell lines.

This investigation sheds light on prognostic factors that impact the survival of patients with newly diagnosed metastatic colon cancer. Nomograms also enable accurate prediction of individual long-term survival for patients with de novo metastatic colon cancer.

P2/3, N=1000, Active, not recruiting, Australasian Gastro-Intestinal Trials Group | Recruiting --> Active, not recruiting

P=N/A, N=100, Recruiting, The Walter and Eliza Hall Institute of Medical Research | Not yet recruiting --> Recruiting

P3, N=1040, Terminated, Swiss Group for Clinical Cancer Research | N=114 --> 1040 | Completed --> Terminated; Board decision in 2020 due to lack of financial funding.

In vivo, oridonin significantly suppressed tumor growth in a xenograft model, accompanied by elevated expression of LC3-II and cleaved caspase-3. Collectively, these findings demonstrated that oridonin could exert potent anti-tumor effects in colon cancer by inducing cell cycle arrest and promoting autophagy-dependent apoptosis via ROS-mediated activation of the AMPK-mTOR-ULK1 signaling pathway.

In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Pan-cancer samples suggested that high RHEBL1 expression facilitates TAM infiltration and is correlated with tumour immunosuppressive status (TCGA). High expression of RHEBL1 may benefit from the therapy of 5-FU, ABT737, Afuresertib, AGI-5198, AGI-6780, and Alisertib.

Immunological studies of the regressed primary tumor and remaining lymph node metastasis instigated a discussion regarding spontaneous regression mechanisms. This case emphasizes the necessity for vigilant clinical management of similar cases because the potential for lymph node metastasis persists even when the spontaneous regression of the primary tumor is observed.

P1/2, N=25, Recruiting, HepaRegeniX GmbH | Not yet recruiting --> Recruiting | Trial completion date: Oct 2025 --> Jul 2026 | Initiation date: Nov 2024 --> May 2025 | Trial primary completion date: Jul 2025 --> Dec 2025