5-fluorouracil

P=N/A, N=36, Recruiting, Dartmouth-Hitchcock Medical Center | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Sep 2026 --> Sep 2027

P2, N=155, Active, not recruiting, University Health Network, Toronto | Trial primary completion date: Apr 2026 --> Dec 2026

CALLY and HALP scores are effective predictors of chemotherapy response and survival in CRC patients with pulmonary metastases receiving FOLFOX. Their combined application enhances risk stratification and may assist in individualized treatment decision-making.

P2, N=150, Not yet recruiting, Verastem, Inc.

In this large real-world cohort, leucovorin significantly improved survival in patients with metastatic colorectal cancer receiving fluorouracil but was associated with increased treatment-related toxicity. These findings support the continued use of leucovorin as a key component of fluorouracil-based chemotherapy regimens.

We analyze resistance across major therapeutic modalities, including chemotherapeutics (5-fluorouracil, oxaliplatin, irinotecan), targeted agents (epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors), and immune checkpoint inhibitors, with mechanistic insights directly linked to actionable, mechanism-guided interventions-including novel targeted agents, rational combination strategies, nanomedicine-based delivery systems, and emerging immunotherapeutic approaches. We further highlight convergent mechanisms that transcend individual therapies, particularly cancer stem cell plasticity and epigenetic reprogramming, which collectively drive multidrug resistance (MDR). Finally, in conjunction with emerging resistance detection technologies such as circulating tumor DNA (ctDNA), this review explores future directions for resistance monitoring and precision treatment adaptation, aiming to provide a systematic reference for overcoming therapeutic resistance in CRC.

A number of agents, including 4a, 4b, 4e, 4g, 6a, and 6b, showed strong hCA IX inhibition (KI = 15.0-37.9 nM), outperforming the reference inhibitor acetazolamide (KI = 25 nM) and displaying better selectivity indices...Compound 4g stood out as the most promising candidate among the investigated derivatives, showing greater activity to 5-fluorouracil during hypoxia and comparable potency under normoxia (IC50 = 5.89 vs. 26.66 µM)...Additionally, favorable pharmacokinetic and drug-likeness features were shown by in silico ADME research. All of these results point to compound 4g as a promising mechanism-based dual VEGFR-2/hCA IX inhibitor with strong anti-colorectal cancer action, especially in hypoxic tumor microenvironment circumstances.

P2/3, N=172, Not yet recruiting, Gruppo Oncologico Del Nord Ovest

Chemosensitivity to gemcitabine and 5-fluorouracil (5-FU) was also evaluated. Knockdown of COLEC12 increased the sensitivity of PC cells to gemcitabine and 5‑FU. This study reveals, for the first time, the tumor-promoting function of COLEC12 in PC and highlights its potential as a therapeutic target in PC.

The CCL3/CCR5 axis drives Oxa resistance in GC by boosting tumor cell survival and fostering immunosuppressive M2 macrophages. Targeting this pathway may offer a strategy to overcome chemoresistance in GC.

P2, N=143, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: May 2027 --> Nov 2027 | Trial primary completion date: Jul 2026 --> Dec 2026

We report a case of metastatic CRC that achieved CR following second-line treatment with FOLFIRI plus ramucirumab after disease progression on first-line FOLFOX plus panitumumab therapy...In the present case, a watch-and-wait strategy was selected to prioritize organ preservation. Given the lack of consensus, further investigation is required to define the optimal strategy for patients achieving CR.