oxaliplatin

Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.

P1/2, N=95, Completed, UCB Biopharma SRL | Active, not recruiting --> Completed

Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.

The inhibitory influence of 3-MA on HMGB1 reversed the influence of Gfi-1 on autophagy and malignant progression in CRC cells. Our study suggested that Gfi-1 inhibited HMGB1 to reduce CRC autophagy levels, increasing CRC sensitivity to L-OHP.

P4, N=36, Recruiting, University of Chicago | Trial completion date: Mar 2026 --> Jun 2025 | Trial primary completion date: Mar 2024 --> Jun 2025

P2, N=207, Active, not recruiting, The Netherlands Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Jul 2029 --> Mar 2029 | Trial primary completion date: Jul 2024 --> Apr 2025

P2, N=130, Not yet recruiting, Second Affiliated Hospital of Guangzhou Medical University

P1, N=12, Not yet recruiting, Astellas Pharma Global Development, Inc.

P1/2, N=40, Recruiting, Seagen Inc. | N=120 --> 40 | Trial primary completion date: May 2024 --> Mar 2025

P2, N=37, Recruiting, Zhejiang Cancer Hospital

P1, N=3, Terminated, National Cancer Institute (NCI) | Active, not recruiting --> Terminated; Due to Covid and poor enrollment

The findings suggest the combination of PD-1-inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow-up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.

P3, N=100, Recruiting, Elisabethinen Hospital

P2, N=30, Recruiting, Chinese PLA General Hospital | Trial completion date: Oct 2023 --> Jun 2025 | Trial primary completion date: Apr 2023 --> Dec 2024

P2, N=46, Not yet recruiting, Fudan University

The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD.

P=N/A, N=36, Recruiting, HK inno.N Corporation

P2, N=50, Recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings.

Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs... Both GSTM1-null and GSTP1 IleVal+ValVal (variant) genotypes are associated with significantly shorter survival in CRC patients. What is more, the GSTM1-null genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.

Recently, hope has been raised regarding the catalytic antioxidants mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5; PledOx®], which by mimicking mitochondrial manganese superoxide dismutase (MnSOD) may be expected to overcome oxaliplatin-associated chemotherapy-induced peripheral neuropathy (CIPN)...However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron paramagnetic resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ in binding to fodipir (DPDP), hence suggesting that the previously reported protective efficacy of MnDPDP against CIPN is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

He was given oxaliplatin plus S-1 therapy...The patient underwent adjuvant chemotherapy with docetaxel plus S-1...He underwent second-line therapy with paclitaxel and ramucirumab...He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases)...Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

P1, N=924, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=260, Recruiting, Genentech, Inc. | Trial completion date: May 2029 --> Dec 2029 | Trial primary completion date: May 2029 --> Dec 2029

The investigational regimen did not improve the primary outcome for the intention-to-treat population but might benefit small subgroups of patients with previously untreated, metastatic microsatellite-stable colorectal cancer.

Flow cytometry analysis revealed increased infiltration of activated cytotoxic (CD8⁺, PD-1⁺) T-cells and anti-tumor cytokines (IFNγ and Granzyme B) in the tumor tissues of the combination therapy group, suggesting that this may be the primary mechanism behind the anti-tumor effect of the combination treatment. These findings indicate that MC-LR regulates the immune stimulation of macrophage polarization and dendritic cell maturation, effectively reversing tumor immunosuppression, activating an anti-tumor immune response, and enhancing tumor therapy.

Combination treatment with leucovorin and oxaliplatin or irinotecan improves the effectiveness of 5FU therapy. In vitro assays with human colon cancer cell lines showed that therapy with TcES+5FU significantly reduced cell proliferation and migration by modulating the P53 and P21 signaling pathways. Our findings demonstrate, for the first time in vivo, that helminth-derived excreted/secreted products may potentiate the effect of 5FU on established colon tumors.

The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

P1/2, N=1126, Recruiting, Amgen | Trial primary completion date: Sep 2026 --> Dec 2026

We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of β-catenin and epithelial-mesenchymal transition (EMT)...Furthermore, even though miR-92a-3p affects ERCC2, XRCC1, E-cadherin, and β-catenin mRNA levels, it has no influence on their protein expression. We found that miR-92a-3p does not upregulate the expression of proteins of DNA-repair pathways and other genes involved in FOLFOX chemotherapy resistance.

We first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.

P2, N=39, Recruiting, Tianjin Medical University Cancer Institute and Hospital

P1/2, N=66, Not yet recruiting, Amsterdam UMC, location VUmc

Here, we revealed the contribution of F. nucleatum to oxaliplatin resistance by inhibiting ferroptosis in CRC. Targeting F. nucleatum and ferroptosis will provide valuable insight into chemoresistance management and may improve outcomes for patients with CRC.

P2, N=25, Not yet recruiting, Mayo Clinic

We presented a case of locally advanced ascending colon cancer in a 17-year-old female patient. CRC rarely occurs in AYAs. However, the incidence has gradually increased in recent years. It should be considered as a differential diagnosis for young patients with long-term abdominal symptoms of unknown cause.

Notably, PDAC-X2 cells demonstrated resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil and oxaliplatin. In conclusion, PDAC-X2 presents an invaluable preclinical model. Its utility lies in facilitating the study of drug resistance mechanisms and the exploration of alternative therapeutic approaches aimed at enhancing the prognosis of this tumour type.

P2, N=150, Recruiting, Leap Therapeutics, Inc. | Trial completion date: Aug 2024 --> Dec 2025 | Trial primary completion date: Mar 2024 --> Dec 2025

P2, N=25, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2021 --> Apr 2024