^
    2d
    COL8A1-positive cancer-associated fibroblasts are drivers of 5-fluorouracil resistance in colorectal cancer. (PubMed, Apoptosis)
    COL8A1⁺Fibs orchestrate 5-FU resistance in CRC via a COL8A1/ITGB1-mediated EMT axis. Disrupting this stromal-tumor crosstalk represents a promising therapeutic strategy to overcome chemoresistance.
    Journal
    |
    COL8A1 (Collagen Type VIII Alpha 1 Chain) • ITGB1 (Integrin Subunit Beta 1)
    |
    5-fluorouracil
    2d
    METTL3 Methylation Induces Decay of Endogenous Retroelement Transcripts to Promote Tumor Immune Evasion. (PubMed, Cancer Res)
    Fluorouracil induced an E2F4/SETD1A/METTL3 regulatory axis, wherein E2F4 self-regulation activated SETD1A to drive METTL3 methylation. Targeting this axis through pharmacological inhibition of E2F4 or genetic disruption of METTL3 methylation cooperated with immune checkpoint blockade (ICB) to significantly suppress tumor growth. These findings unveil a methylation-dependent regulatory mechanism that reshapes the tumor immune microenvironment, offering a therapeutic strategy for CRC.
    Journal
    |
    METTL3 (Methyltransferase Like 3) • SETD1A (SET Domain Containing 1A)
    |
    5-fluorouracil
    2d
    AK112 and Chemotherapy in First-line Metastatic Colorectal Cancer (clinicaltrials.gov)
    P3, N=560, Recruiting, Akeso | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Avastin (bevacizumab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • Yidafan (ivonescimab)
    2d
    A Phase Ib/II Clinical Study on AK112 Combined or Not Combined With AK119 in pMMR/MSS Colorectal Cancer (clinicaltrials.gov)
    P1/2, N=170, Active, not recruiting, Akeso | Recruiting --> Active, not recruiting
    Enrollment closed • pMMR
    |
    MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • Yidafan (ivonescimab) • drebuxelimab (AK119)
    2d
    CIME/ET23-185: Study aiming to compare the survival of patients with locally advanced or metastatic MSI/dMMR Esogastric adenocarcinomas treated by a combination of Immune checkpoint inhibitors (botensilimab + balstilimab) versus the standard of care (FOLFOX/XELOX + nivolumab) (2023-506291-28-00)
    P2/3, N=132, Recruiting, Centre Leon Berard | Not yet recruiting --> Recruiting
    Enrollment open • Checkpoint inhibition • dMMR
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
    |
    PD-L1 expression • MSI-H/dMMR • HER-2 negative
    |
    Opdivo (nivolumab) • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium • balstilimab (AGEN2034) • botensilimab (AGEN1181)
    2d
    BOLD-100-001: BOLD-100 in Combination with FOLFOX for the Treatment of Advanced Solid Tumours (2024-517500-11-00)
    P1/2, N=52, Recruiting, Bold Therapeutics Inc. | N=38 --> 52
    Enrollment change
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF wild-type
    |
    5-fluorouracil • oxaliplatin • leucovorin calcium • BOLD-100
    2d
    A Study of Nivolumab Combined With FOLFOX and Regorafenib in People Who Have HER2-Negative Esophagogastric Cancer (clinicaltrials.gov)
    P2, N=39, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • 5-fluorouracil • Stivarga (regorafenib) • oxaliplatin • leucovorin calcium
    3d
    LUCERNA: A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer (clinicaltrials.gov)
    P3, N=500, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Dec 2029 --> Sep 2028 | Trial primary completion date: Dec 2029 --> Sep 2028
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • CLDN18 (Claudin 18)
    |
    MSI-H/dMMR • HER-2 negative
    |
    Keytruda (pembrolizumab) • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium • Vyloy (zolbetuximab-clzb)
    3d
    FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, Oncolytics Biotech
    New P2 trial
    |
    MSI (Microsatellite instability)
    |
    RAS mutation
    |
    Avastin (bevacizumab) • 5-fluorouracil • irinotecan • leucovorin calcium • Reolysin (pelareorep)
    3d
    FOLFOX Chemotherapy Combined With Fruquintinib and Serplulimab as First-Line Conversion Therapy for Initially Unresectable pMMR/MSS Colorectal Cancer (clinicaltrials.gov)
    P4, N=42, Not yet recruiting, Ye Xu
    New P4 trial • Tumor mutational burden • pMMR
    |
    MSI (Microsatellite instability)
    |
    5-fluorouracil • oxaliplatin • Fruzaqla (fruquintinib) • leucovorin calcium • Hetronifly (serplulimab)
    3d
    Neoadjuvant camrelizumab combined with metronomic chemotherapy in patients with advanced esophageal squamous cell carcinoma: a pilot randomized phase 2 trial. (PubMed, BMC Med)
    Neoadjuvant MCT combined with camrelizumab led to an increased pCR rate (54.5 vs. 16.7%) in ESCC patients compared to MCT alone. This combination therapy may offer a promising approach for enhancing cancer treatment outcomes.
    Clinical • P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    ENTPD1 (Ectonucleoside Triphosphate Diphosphohydrolase 1)
    |
    cisplatin • paclitaxel • 5-fluorouracil • AiRuiKa (camrelizumab)