5-fluorouracil

P1/2, N=480, Recruiting, Parabilis Medicines, Inc. | N=245 --> 480

P1/2, N=21, Not yet recruiting, University of Kansas Medical Center

P2, N=78, Recruiting, Sun Yat-sen University

P1/2, N=50, Active, not recruiting, Anup Kasi | Recruiting --> Active, not recruiting | Phase classification: P1b/2a --> P1/2 | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2023 --> Sep 2025

P1, N=542, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

In this study, mice harboring CT26 tumors were divided into four groups, each administered with either XHP monotherapy, 5-fluorouracil (5-FU), or a combination of both...This study delineates a potential mechanism by which XHP inhibits CRC tumorigenesis through modulating the gut microbiota, serum metabolites, and reshaping the tumor immune microenvironment in a murine CRC model. These findings contribute to a more profound understanding and potentially broaden the clinical utility of XHP in oncology.

It is universally treated with a combination of the DNA damaging chemotherapy drugs irinotecan, 5-Fluorouracil (5-FU), and oxaliplatin. Finally, the combination of low doses of OTI-611 with irinotecan significantly reduces tumor volume and extends survival in CRC xenograft mouse models compared to irinotecan alone. The combination of standard of care chemotherapy drugs with CHD1Li represents a promising advancement in future therapeutic strategies for CRC and other cancers driven by CHD1L.

Furthermore, Rc exerts anti-inflammatory and anti-apoptotic effects through PI3K-AKT and NF-κB signaling pathways. In conclusion, ginsenoside Rc demonstrated significant protective effects against 5-Fu-induced intestinal mucositis via the PI3K-AKT/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for chemotherapy-related mucositis.

One of the most used chemotherapy agents in clinical practice is 5-Fluorouracil (5-FU), a fluorinated pyrimidine in the category of antimetabolite agents...Overall, our data indicated Ulva pertusa to be a promising therapeutic against 5-FU's adverse effects, therefore, it could be worthwhile to investigate the possibility of using this alga in safer cancer treatment formulations. Certainly, future preclinical and clinical studies could assess the alga's efficacy in diverse cancer treatment regimens, exploring its role as an adjuvant therapy that may reduce chemotherapy-related toxicity without compromising therapeutic outcomes.

FOLFIRI (5-FU, leucovorin, irinotecan) is the first-line chemotherapy for metastatic colorectal cancer (mCRC), but response rates are under 50%...In conclusion, the REO-based signature effectively identifies mCRC patients likely to benefit from FOLFIRI. Furthermore, these signature genes may play a crucial role in the chemotherapy.

Conclusion. These results demonstrated a hierarchical network of gut injury mechanisms differentially regulated in the course of the emergence of 5-FU-induced mucositis.

Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

P2, N=78, Recruiting, Akeso | Not yet recruiting --> Recruiting | N=60 --> 78 | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

Triplet induction chemotherapy is a treatment of choice in selected patients with SMRC, allowing to adapt the therapeutic strategy to the response and invasiveness of the various sites.

P2, N=80, Recruiting, Lisata Therapeutics, Inc. | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

P2, N=73, Not yet recruiting, UNICANCER | Initiation date: Oct 2024 --> Jan 2025

P1/2, N=30, Not yet recruiting, Lisata Therapeutics, Inc. | Trial completion date: Jun 2027 --> Sep 2027 | Initiation date: Dec 2024 --> Mar 2025 | Trial primary completion date: Jun 2027 --> Sep 2027

P3, N=238, Recruiting, Gruppo Oncologico del Nord-Ovest

This study validated the role of YAP as an oncogene in CRC, as it promoted chemoresistance through the mTOR/GLUT3 axis. These results suggested YAP as a potential target for promoting the efficacy of chemotherapy in patients with CRC.

This study aimed to understand the evolution of cognitive changes following methotrexate (MTX) or 5- fluorouracil (5-FU) chemotherapy, assessing three time-points: acute (96-hour), sub-acute (31-days) and chronic (93-days). These results provide valuable insight into the complexity of a mediator of neuroinflammation in CICI. While neuroinflammation may be a promising therapeutic target, further markers should be assessed to elucidate the full neuroimmune response, and thus which aspects to target and when, to ensure optimal outcomes for cancer patients treated with chemotherapy.

Compared with parental cells, the levels of UBE2T were also dramatically elevated in oxaliplatin (OXA)- and 5-fluorouracil (5-FU)-resistant colorectal cancer cells. To conclude, UBE2T confers chemoresistance of colorectal cancer by boosting the signal propagation of the Wnt/β-catenin pathway in an ERK-dependent manner. Therefore, UBE2T could be a potential target for overcoming chemoresistance in the treatment of colorectal cancer.

P1, N=321, Recruiting, Inhibrx Biosciences, Inc | N=240 --> 321 | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P2/3, N=429, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=36, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P=N/A, N=200, Enrolling by invitation, Helsinki University Central Hospital | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2020 --> Dec 2027

P1/2, N=6, Terminated, ImmunityBio, Inc. | N=80 --> 6 | Unknown status --> Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

P3, N=1147, Recruiting, Bristol-Myers Squibb | N=831 --> 1147 | Trial primary completion date: Jun 2025 --> Aug 2024

P2, N=110, Not yet recruiting, Qilu Hospital of Shandong University

A model antigen-ovalbumin (OVA257-264) was further conjugated to C2.2 to construct C2.2-OVA and a model chemotherapy-Doxorubicin (DOX) was also loaded to C2.2-OVA to prepare DOX@C2.2-OVA for the combined chemo- and immunotherapy to treat breast cancer...Although C2.2 showed no cytotoxicity, C2.2 increased the potency of 5-FU and carboplatin to MCF-7 and 4 T1 breast cancer cells. DOX@C2.2-OVA treatment to 4 T1 tumor in vivo showed the significant reduction of tumor size and weight, and resulted in more DCs and CD8+ T cells in 4 T1 tumor. In summary, DOX@C2.2-OVA that could be inserted into tumor cell plasma membrane enhanced the combined chemo- and immunotherapy for the breast cancer treatment.

PAD4 appeared to be constitutively expressed in tumor-infiltrating neutrophils but not in GC cells. Our findings highlight unique roles of PAD4, in which origin-dependent PAD4 might work complementarily on the progression and treatment vulnerability of GC.

Importantly, the epithelial phenotype induced by low-dose Vit C rendered CR-CSCs sensitive to conventional treatments, enhancing chemosensitivity to Cisplatin, Paclitaxel, and 5-Fluorouracil by 60%-90%. These findings suggest that low dose Vit C could serve as an adjuvant to conventional therapeutic strategies for targeting advanced colorectal cancer by sensitizing CR-CSCs to chemotherapy and potentially reducing tumor recurrence.

P1/2, N=2, Terminated, ImmunityBio, Inc. | Phase classification: P1b/2 --> P1/2 | N=332 --> 2 | Active, not recruiting --> Terminated; low enrollment

This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC...Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC.

The most potent compound in the series outperformed tamoxifen and 5-fluorouracil, with selectivity indices (SI) of 1.60 and 1.99 against MDA-MB-468 and MDA-MB-231 cancer cells, respectively. The Caspase 3/7 7-AAD assay showed live cell populations of 72.10% and 49.20% after 24 and 48 hours, respectively, indicating that the cytotoxic effect is mediated through the caspase apoptotic pathway. Molecular docking studies further suggested the compound's potential as an EGFR inhibitor, highlighting its promise as a therapeutic agent.

P3, N=1000, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | Trial completion date: Jan 2032 --> Dec 2032

However, we found that 100% (2/2) of patients carrying the homozygous variant (GG) DPYD*5, presented no significant toxicity, so, DPYD*5 may be a predictive marker of neutropenia in patients treated with 5-FU. These outcomes suggest that there may be an increased risk of developing 5-FU-induced neutropenia in patients carrying the DPYD*9A, which should be considered as part of the standard procedure.

P=N/A, N=10, Recruiting, University of Auckland, New Zealand | Not yet recruiting --> Recruiting | Trial primary completion date: Jan 2025 --> Jul 2025

While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen.

Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells.

Importantly, the combination of CAt and 5-fluorouracil (5-FU) exhibited synergistic growth suppression and attenuated the development of 5-FU resistance. Overall, the findings suggest that CAt holds promise as a potential drug or adjuvant to improve melanoma treatment.

5-Fluorouracil (5-Fu) is a widely used anticancer drug for various cancers, but the development of 5-Fu resistance poses a challenge in treating cervical cancer patients...Finally, combining FGD5-AS1 silencing with 5-Fu treatments resulted in a synergistic inhibitory effect (CI < 1) on the viability of cervical cancer cells. This study reveals a FGD5-AS1-miR-130a-3p-YTHDF2 axis that could be a promising therapeutic target for overcoming 5-Fu resistance in cervical cancer.

The standard CRC chemo drug, 5-Fluorouracil (5-FU), has a poor response rate and chemoresistance, prompting the need for a more effective and affordable treatment...Similarly, fecal acetate concentration was upregulated by Prohep. To sum up, Prohep demonstrated exceptional anti-tumorigenesis effects in the AOM/DSS model, which revealed its potential to develop into a novel CRC therapeutic in the future.