P1/2, N=32, Recruiting, Australasian Leukaemia and Lymphoma Group | Not yet recruiting --> Recruiting

P2, N=29, Completed, Virginia G. Kaklamani | Unknown status --> Completed

These data support further clinical development for the combination of copanlisib and eribulin. These data led to a phase I/II trial of copanlisib and eribulin in patients with metastatic TNBC.

P2, N=74, Recruiting, Fudan University

These findings provide an epigenetic mechanism of action of eribulin, supporting its use early in the disease process for MET induction to prevent metastatic progression and chemoresistance. These findings warrant prospective clinical evaluation of the chemosensitizing effects of eribulin in the treatment-naive setting.

P2, N=10, Not yet recruiting, Fudan University

P2; Changes in ctDNA can occur rapidly and reflect changes in patients' clinical tumour responses (NCT02681523).

This study sheds light on the tumour-suppressive role of TINCR in PANC-1 cells and suggests its potential as a therapeutic target. These results shed light on the molecular mechanisms underlying the impact of TINCR on pancreatic cancer and offer promising opportunities for innovative therapeutic strategies to improve outcomes in this serious malignancy.

We found that eribulin-induced cell death was reduced by ferroptosis inhibitors; deferoxamine, an iron chelator and ferrostatin-1, a lipid peroxidation inhibitor...The combination of eribulin and ML210, a glutathione peroxidase 4-inhibiting ferroptosis inducer, had a synergistic effect on ferroptosis. Taken together, our findings show firstly that eribulin triggers ferroptosis in OCCC and this effect occurs via the suppression of the Nrf2-HO-1 signaling pathway, SOD activity and the promotion of lipid peroxidation. These findings suggest that eribulin-induced ferroptosis is associated with its anti-tumor effect and also could be a potential therapeutic target in OCCC.

Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the β-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.

P1, N=181, Recruiting, Eisai Inc. | Trial completion date: Oct 2024 --> Mar 2027 | Trial primary completion date: Oct 2024 --> Mar 2027

P1, N=8, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P1, N=15, Active, not recruiting, OHSU Knight Cancer Institute | Phase classification: P1b --> P1

P2, N=81, Not yet recruiting, Zhejiang Cancer Hospital

P2, N=30, Recruiting, Criterium, Inc. | Trial completion date: May 2025 --> Aug 2027 | Trial primary completion date: Nov 2023 --> Jun 2027

We also observed differential gene expression and induced immune cell infiltration in tumors pretreated with ICG-001 and then treated with CAR T cells as compared with single treatment groups or when ICG-001 treatment was administered after CAR T cell therapy. We conclude that specific Wnt/CBP/β-catenin antagonism results in pleotropic changes in the glioma TME, including glioma stem cell differentiation, modulation of the stroma, and immune cell activation and recruitment, thereby suggesting a possible role for enhancing immunotherapy in glioma patients.

P1, N=70, Active, not recruiting, Eisai Co., Ltd. | Recruiting --> Active, not recruiting

CDH4 induces PTC angiogenesis and metastasis via the inhibition of β-TrCP1-dependent ubiquitination of β-Catenin.

Furthermore, it is identified that ILKAP functions by mediating binding between TCF4 and β-catenin to enhance expression of WNT target genes. Taken together, the study demonstrates a critical function of ILKAP in metastasis of HCC, since ILKAP is crucial for the activation of the WNT pathway via stabilization of β-catenin and increased binding between TCF4 and β-catenin.

P3, N=302, Recruiting, Sun Yat-sen University

P3, N=170, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

Nur77 agonist Csn-B effectively enhanced the therapeutic effect of cisplatin on HB tumors both in vitro and in vivo. This study confirms that Nur77 may act as an oncogene in HB tumors and mediate the progression of HB by inhibiting the expression of β-catenin, which provides a new targeted therapy for the clinical treatment of HB patients; meanwhile, the combination of Nur77 agonist and cisplatin treatment may improve the chemotherapeutic efficacy of HB patients, which provides a new idea for the improvement of the clinical prognosis of HB patients.

P2; Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1/2, N=132, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Aug 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

P3, N=170, Suspended, National Cancer Institute (NCI) | N=465 --> 170

Materials & MDA-MB 231 cells were treated with eribulin and paclitaxel, and the samples from 53 patients treated with neoadjuvant eribulin were compared with those from 14 patients who received the standard-of-care treatment using immunohistochemistry. Eribulin treatment caused significant DNA methylation changes in drug-tolerant persister TNBC cells, and it also elicited changes in the expression levels of epigenetic modifiers (DNMT1, TET1, DNMT3A/B) in vitro and in primary TNBC tumors. These findings provide new insights into eribulin's mechanism of action and potential biomarkers for predicting TNBC treatment response.

P1, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=54 --> 9 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Consistent with this notion, β-catenin inhibition using XAV939 or ICG-001 partially prevented centrinone-induced death and rescued the growth two APC-mutant organoid lines tested. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in a subset of APC-mutant colorectal cancer independently of the classical p53 pathway.

Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered...Capecitabine was selected for treatment of the recurrent lesion...At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT)...Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity)...About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.

Our real-world study suggests that eribulin may be a potential treatment option for MBC patients who fail a prior PI3K inhibitor.

Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with GC, and no new safety signals were observed, compared with either monotherapy.

In vivo, knockdown of NORAD led to the reduction of inflammatory cell infiltration and collagen deposition, suppression of IL-4, IL-13, transforming growth factor-β1 and immunoglobulin E production, decreasing of N-cadherin, chromosome condensation 2, β-catenin and c-Myc expression, but increasing of E-cadherin and miR-410-3p expression. Silencing of NORAD alleviated epithelial-mesenchymal transition-mediated airway remodeling in asthma via mediating miR-410-3p/chromosome condensation 2/Wnt/β-catenin pathway.

The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.

FHL1 is downregulated in PTC and its expression is associated with better clinical outcomes for patients with the disease. FHL1 acts as a tumor suppressor via, at least partially, suppressing Wnt/β-catenin pathway.

Results show complex synergistic interactions between eribulin, fulvestrant, and palbociclib, and point to a particularly robust synergy when combining all three drugs.

P1/2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=30, Recruiting, Australia New Zealand Gynaecological Oncology Group

P2, N=252, Recruiting, Guangdong Provincial People's Hospital | Not yet recruiting --> Recruiting

Overall, these results support a model wherein resistomycin inhibits Wnt/β-catenin signaling within CRC cells, thereby inducing apoptotic death. Further research may be warranted to better clarify the potential utility of this compound as a candidate drug for use in the treatment of patients suffering from this form of cancer.

Other drugs, such as imatinib, figitumumab, axitinib, and eribulin, are also being tested. Definitive radiotherapy appears to be a promising therapeutic modality. Since standards for the treatment of advanced and metastatic diseases are not available, further investigation of novel agents is necessary.

Experimental and bioinformatic data confirmed the relation between Wnt signaling and glycolytic enzymes in tongue cancer cells and HNSCC clinical samples. Overall, the inhibition of glucose metabolism by Wnt signaling inhibitors is a promising mode of action against tongue cancer cells.

Of the drugs used in second-line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L-sarcoma), eribulin for liposarcoma, and pazopanib for non-liposarcoma. The present study demonstrated the potential of tailored therapy guided by mutation profiles established by comprehensive genomic profiling testing in optimizing second-line chemotherapy for STS. The findings of this study will hopefully contribute some valuable insights into enhancing STS treatment strategies and outcomes.