P=N/A, N=110, Active, not recruiting, Nantes University Hospital | Recruiting --> Active, not recruiting | Trial completion date: Oct 2026 --> Mar 2026 | Trial primary completion date: May 2026 --> Nov 2025

P=N/A, N=150, Not yet recruiting, Rajiv Gandhi Cancer Institute & Research Center, India

Importantly, CBD-induced TRPA1 activation sensitized CRC cells to oxaliplatin, triggering apoptotic-not senescent-cell death...Our findings reveal a non-canonical bioelectric-lysosomal axis that links TRPA1 activity to NRF2 destabilization in colorectal cancer. This work expands the understanding of NRF2 proteostasis under sustained oxidative stress and highlights TRPA1 as a tractable redox-modulating target for overcoming chemoresistance.

P2, N=90, Not yet recruiting, Shanghai Zhongshan Hospital

The FOX regimen based on 5-fluorouracil (5-FU) and oxaliplatin (OX), a standard therapy for CRC, paradoxically induces both detrimental upregulation of CD47 and beneficial microsatellite instability (MSI). Notably, these effects are achieved at half the FOX dosage with minimal systemic toxicity. This study highlights the potential of nano-immunotherapeutic drugs that function as chemotherapeutic feedback modulators, offering a promising avenue for heterogeneous and immunotherapy-resistant MSS-CRC.

High pretreatment NORAD expression is an independent risk factor for poor response to neoadjuvant chemotherapy. Downregulating NORAD restores oxaliplatin sensitivity in resistant cells.

This analysis of a phase II randomized trial included patients with gastric adenocarcinoma treated with Menadione plus XELOX or XELOX alone. PFS analysis showed a higher risk of progression in No-CTC responders, with HRs of 2.28 at 3 months and 10.5 at 15 months (p < 0.001). Patients without CTC response had worse OS and PFS in both treatment groups, suggesting that CTC response could be a valuable predictor of clinical outcomes, warranting more intensive monitoring and tailored therapies for specific subgroups.

The results indicated that PFOA and PFOS significantly increased the resistance of HCT116 and SW620 cells to Oxaliplatin (OXA), 5-Fluorouracil (5-FU), and Irinotecan (CPT-11). Further studies revealed that PFOA and PFOS reverse the cell cycle arrest effect of chemotherapeutic drugs on CRC cells by regulating the expression of Cyclin A2 and CDK2. Exposure to PFAS may potentially elevate the risk of chemotherapy resistance in CRC, a finding that has significant implications for clinical treatment and chemical risk assessment.

Therefore, our findings suggest that JUP promotes PDAC tumorigenesis and progression through FOXM1-JUP transcriptional axis and the combination of FOXM1 and JUP be a more precise biomarker for targeted therapy and prognostic prediction, nominating this dyad as an actionable vulnerability for molecularly targeted interventions in PDAC.

Compound 8d exhibited 2.7- to 192-fold enhanced potency compared to precursor compounds 4 and 3d, as well as the clinical agents oxaliplatin, doxorubicin, and cisplatin. These effects synergistically induced immunogenic cell death (ICD), promoting dendritic cell (DC) maturation and enhancing CD8+ T lymphocyte infiltration into the tumor microenvironment (TME), thereby potentiating antitumor immunity. Collectively, 8d exerted potent antitumor effects through combined chemotherapeutic and immunotherapeutic mechanisms, highlighting its potential as a promising candidate for cancer therapy.

In this study, we devised a localized chemo-immunotherapeutic strategy by co-loading the chemotherapeutic drug, oxaliplatin (OXA), and the immune-checkpoint blockade (ICB) antibody, anti-programmed cell death protein ligand 1 (anti-PD-L1), into a matrix metalloproteinase (MMP)-responsive injectable poly(L-glutamic acid) hydrogel (MMP-gel)...Moreover, the OXA&anti-PD-L1@MMP-gel effectively inhibited the growth of distal tumors in a bilateral-tumor experiment. Consequently, the responsive hydrogel-based chemo-immunotherapy holds potential in tumor treatment.

Loss of CCN2 expression markedly attenuated cell proliferation, migration, invasion, and oxaliplatin resistance compared with control cells...Collectively, these findings suggest that CCN2 functions as a central regulator of stemness and malignant potential in CRC and may represent a promising therapeutic target to prevent recurrence and metastasis. Additional mechanistic studies are warranted to further elucidate the molecular pathways of CCN2 and to validate the role of APOC2 in liver-metastatic CRC stem cells.