P=N/A, N=60, Not yet recruiting, Mazandaran University of Medical Sciences

P4, N=6, Completed, Radboud University Medical Center | Phase classification: P2 --> P4

The case provides additional support that IT pemetrexed can offer symptomatic relief and may be considered as a treatment option in advanced LM. Furthermore, the case illustrates that an increased dose of lorlatinib may efficiently control LM in patients with ALK-rearranged NSCLC, following progression on standard lorlatinib dosage.

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.

Capecitabine enhances miR-29b-3p expression, leading to the downregulation of MMP16, thereby inhibiting proliferation and promoting apoptosis in ovarian cancer cells.

PTOV1 and Cyfra21-1 are upregulated in LUAC patients who are resistant to neoadjuvant chemotherapy. Both markers not only have predictive value for chemosensitivity in these patients, but are also independent factors affecting neoadjuvant chemosensitivity.

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.

P1/2, N=57, Not yet recruiting, Asan Medical Center

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.

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

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.

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.

P=N/A, N=220, Recruiting, Affiliated Hospital of Qinghai University | Not yet recruiting --> Recruiting

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

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.

A total of 21 patients with advanced HER2-negative GC, who had progressed after receiving standard first-line regimens [tegafur, gimeracil and oteracil potassium capsules (S-1) or capecitabine plus oxaliplatin], were selected. The present study retrospectively analyzed the new second-line approach of PD-1 inhibitor combined with taxanes for HER2 negative GC which effectively improved patient PFS and OS compared with single-agent chemotherapy. The expression levels of Ki67 and the tumor marker-negative status possess potential clinical value in monitoring prognosis and guiding future individualized use of chemotherapy combined with immunotherapy.

Although current first- and second-line therapies stratify for KRAS/NRAS/BRAF mutations, microsatellite instability, tumour location and co-morbidities, the therapeutic mainstay for the first- and second-line treatment of the majority of patients consists of 5-fluorouracil (5-FU)-based chemo-immunotherapy. By exchanging the chemotherapeutic combination partner from oxaliplatin to irinotecan or vice versa, plus the additive anti-epidermal growth factor receptor/anti-vascular endothelial growth factor antibody, the negative factor of non-response to first-line therapy could not be overcome by second-line treatment in this study population. These findings must be confirmed in larger studies, but indicate the need for novel treatment options, especially for patients not responding to first-line 5-FU-based chemo-immunotherapy.

Furthermore, suppressing GDF15 can increase the sensitivity of MSI-H CRC cells to 5-fluorouracil (5-FU), which decreases cell viability and increases the apoptosis rate...Our research indicates that inhibiting GDF15 affects ferroptosis-related pathways, leading to ferroptosis and improving the MSI-H CRC response to 5-FU therapy. As a result, GDF15 could be a promising target for diagnosing and treating MSI-H CRC, potentially enhancing the overall effectiveness of therapy for patients with MSI-H CRC.

However, the GX regimen should be considered in patients who cannot tolerate hematological toxicity. ClinicalTrials.gov identifier: NCT02207335.

Eligible patients will be registered and receive three cycles of oxaliplatin and S-1 (SOX) regimen in combination with cadonilimab...The results of the study may provide more evidence for neoadjuvant immunotherapy combined with chemotherapy in locally advanced G/GOJ adenocarcinoma. ClinicalTrials.gov, NCT05948449.

Multi-omics and treatment response data from 115 samples of 49 patients with CRLM undergoing bevacizumab (BVZ)-based chemotherapy show little difference in genomic alterations in 92% of cases, while remarkable differences are observed at the transcriptomic level...Gene interference experiments suggest that SMAD4R361H/C mutations confer BVZ and 5-fluorouracil (5-FU) resistance through STAT3 signaling. Notably, supplementing BVZ and 5-FU with the STAT3 inhibitor GB201 restores therapeutic efficacy in SMAD4R361H/C cancer cells. Our study uncovers the evolutionary dynamics of CRLM and its microenvironment during treatment and offers strategies to overcome drug resistance.

BATF2 plays a pivotal role in regulating stem-like characteristics and chemoresistance in gastric cancer through the BATF2/PTEN/AKT/ABCG2 pathway. These findings suggest a novel therapeutic strategy targeting BATF2 to enhance chemotherapy effectiveness in gastric cancer treatment.

Clinical treatment of hepatocellular carcinoma (HCC) with 5-fluorouracil (5-FU), the primary anticancer agent, remains unsatisfactory due to the glutathione (GSH)-associated drug resistance and immunosuppressive microenvironment of HCC...Most importantly, FU-SS-IND NPs could upregulate programmed death ligand 1 (PD-L1) expression on the surface of tumor cells, which enables facile combination with immune checkpoint blockade (ICB) for a ultimate prolonged survival lifetime of 5-FU-resistant tumors-bearing mice. Overall, the minimalist bioreducible nano-prodrug developed herein demonstrates great translatable potential for efficiently reversing drug resistance and enhancing immunotherapy of HCC.

After Oxaliplatin combined with S-1 regimen, the effect was up to PR...The combined application of S-1 and Apatinib in gastric cancer maintenance therapy deserves further study. Maintenance therapy for gastric cancer has attracted wide attention, and more large-scale clinical research is under way.

P=N/A, N=110, Active, not recruiting, GERCOR - Multidisciplinary Oncology Cooperative Group | Unknown status --> Active, not recruiting | Trial completion date: Oct 2020 --> Jan 2025

P3, N=234, Active, not recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> Aug 2024

P3, N=29, Terminated, Peking University Cancer Hospital & Institute | N=564 --> 29 | Recruiting --> Terminated; The number of patients enrolled was much less than expected

P2, N=45, Completed, Georgetown University | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> May 2024

P2, N=64, Recruiting, Northwestern University | Not yet recruiting --> Recruiting | Initiation date: May 2025 --> Nov 2024