5-fluorouracil

P=N/A, N=180, Completed, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Trial completion date: Sep 2029 --> Dec 2025 | Trial primary completion date: Sep 2027 --> Sep 2025 | Enrolling by invitation --> Completed

Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and higher IL-18 expression in pancreatic tumors is associated with poor prognosis. On the other hand, the release of active IL-18 was not observed with gemcitabine. These findings suggest that a low-nutrient tumor microenvironment and 5-FU therapy can promote caspase-8-dependent pyroptotic cell death with IL-18 activation, potentially contributing to chronic inflammation in pancreatic tumors.

NCT05286814 is a phase II non-randomized trial evaluating subcutaneous PDS01ADC in combination with HAIP floxuridine and systemic chemotherapy (FOLFOX or FOLFIRI) in patients with unresectable microsatellite stable or mismatch repair-proficient colorectal liver metastases previously treated with at least one line of systemic chemotherapy...Addition of PDS01ADC is not detrimental to HAIP therapy and is associated with both systemic and intratumoral immune modulation. Initial results warrant continuation to full enrollment for further evaluation of clinical and scientific endpoints.

These findings establish the COP1-LUZP1-MYL9 axis as a therapeutic target for CRLM and oxaliplatin-based chemoresistance. Clinically, COP1 expression profiling in PDOs from postoperative specimens enables a precision strategy for managing oxaliplatin-based chemoresistance, especially in the context of FOLFOX.

P2/3, N=30, Not yet recruiting, Rakuten Medical Inc.

5-Fluorouracil (5-FU) and its prodrugs are widely used drugs for chemotherapy in various cancers. In conclusion, our study reveals that everolimus sensitizes breast cancer to fluoropyrimidines by destabilizing TYMS through modulation of its O-GlcNAcylation. These findings support a promising combination strategy to improve the therapeutic efficacy of 5-FU and capecitabine in breast cancer.

P2/3, N=220, Not yet recruiting, Shanghai 10th People's Hospital

Targeting FASN as a modulator of 5-FU resistance, via pharmacological inhibitor and phototoxic peptide conjugate, resensitised cells to 5-FU in acquired organoid models of resistance. PDOs are valuable tools for modelling drug resistance and offer opportunities to discover novel therapeutic approaches to circumvent the emergence of drug resistance.

Low BLM RNA expression is associated with improved survival after treatment with DNA-damaging agents, whereas low RAD51 expression shows a favorable but nonsignificant trend. These findings are exploratory and suggest that RNA-based HR gene expression may warrant further investigation as a potential prognostic biomarker in metastatic CRC.

P2, N=83, Active, not recruiting, Vejle Hospital | Trial completion date: Dec 2025 --> Dec 2026

Notably, baseline NR3C1 methylation levels predicted response to first-line FOLFIRINOX-based treatment with an acceptable 75% sensitivity and a high specificity of 92.86%. These findings highlight the clinical significance of cfDNA methylation as a minimally invasive biomarker source, emphasizing LAX1, NR3C1, and RCAN3 as prognostic biomarkers in mPDAC. Specifically, baseline NR3C1 methylation emerges as a promising predictor of treatment response, supporting personalized therapeutic strategies in mPDAC.

P2/3, N=690, Recruiting, Bristol-Myers Squibb | N=184 --> 690