P2, N=12, Recruiting, Sun Yat-sen University

In the analysis using human- leukemia monocytic cell, the concentration of eribulin released from TROP2-eribuilin was significantly reduced by the use of an Fc receptor inhibitor (P < 0.05). These results revealed that Fcγ-receptor-mediated uptake by alveolar macrophages releases cytotoxic payload into lung tissue, helping to clarify the pathogenesis of ADC-induced ILD.

P1/2, N=89, Completed, Eisai Inc. | Active, not recruiting --> Completed

The study suggests that S. herbacea, a prebiotic, effectively suppresses CRC progression, with limited additional benefits from combining with probiotics. These findings underscore the therapeutic potential of prebiotics in CRC.

P1, N=158, Recruiting, Alnylam Pharmaceuticals | Not yet recruiting --> Recruiting

Subgroup analysis was conducted on chemotherapy regimens, with and without eribulin. Despite variations in chemotherapy regimens, patients with ABC or MBC and high ALC exhibited longer PFS and PPS (HR = 0.45, 95% CI: 0.30-0.67, P < 0.0001), PFS and TTF (HR = 0.39, 95% CI: 0.20-0.78, P = 0.008), and OS (HR = 0.71, 95% CI: 0.62-0.82, P < 0.00001; HR = 0.5, 95% CI: 0.35-0.70, P < 0.0001). The results of this meta-analysis suggest that baseline ALC, as an immune marker, can serve as an effective prognostic indicator for ABC or MBC.

P1/2, N=301, Recruiting, Eisai Inc. | Phase classification: P1 --> P1/2 | N=181 --> 301 | Trial completion date: Mar 2027 --> Nov 2026 | Trial primary completion date: Mar 2027 --> Nov 2026

To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.

ErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001...Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

P2, N=16, Completed, Italian Sarcoma Group | Recruiting --> Completed | Trial completion date: Apr 2024 --> Sep 2024 | Trial primary completion date: Apr 2024 --> Sep 2024

P1, N=158, Not yet recruiting, Alnylam Pharmaceuticals

P1, N=33, Not yet recruiting, National Cancer Institute (NCI)

P1/2, N=6, Terminated, M.D. Anderson Cancer Center | N=25 --> 6 | Trial completion date: Dec 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Sep 2024; The sponsor terminated support for this study

P2, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Consistently, the miR139a-5p mimic enhanced the suppression of β-catenin, c-Myc, and HK2, while the miR193a-5p inhibitor reversed the ability of GF2 to attenuate the expression of β-catenin, c-Myc, and HK2 in HeLa cells. Overall, these findings suggest that GF2 induces apoptosis via the activation of miR193a-5p and the inhibition of β-catenin/c-Myc/HK signaling in cervical cancer cells.

This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options.

Moreover, GLI1 knockdown combined with ICG-001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β-catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients.

P3, N=201, Suspended, Academic and Community Cancer Research United | Trial completion date: Dec 2023 --> Oct 2024

Eribulin and capecitabine sensitivity may vary based on HER2 expression in patients with HER2-low and HER2-null breast cancer. Prognosis was similar between the HER2-low and the HER2-null groups.

Further analyses indicate that anlotinib plus eribulin treatment results in micro-vessel density and PD-L1 expression alterations, suggesting a potential impact on the tumor microenvironment. This study extensively explored the combination regimen at multiple levels and its underlying molecular mechanism in RLPS, thus providing a foundation for translational medicine research.

These findings establish the sphingolipid metabolic enzyme SPHK1 as a regulator of TKI sensitivity and suggest that combining SPHK1 inhibition with TKIs could be an effective approach for treating FLT3-mutated AML.

Using eribulin in the first- or second-line may demonstrate the non-inferiority of HRQoL compared to S-1, an oral 5-fluorouracil derivative, while maintaining OS. The time of the first clinical deterioration was similar between the two groups and OS significantly increased in eribulin-treated patients. This study was funded by CSPOR-BC and Eisai CO., Ltd.

Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.

P2, N=10, Recruiting, Sun Yat-sen University

CHL-C is capable of inducing apoptosis and autophagy by influencing the Wnt/β-catenin signaling pathway.

The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway.

More importantly, compound 10 exhibits favorable pharmacokinetic parameters and significant anti-tumor efficacies in the HCT116 xenograft model. Taken together, this study furnished the discovery of candidate drug compound 10 possessing a novel fused tetrahydroisoquinoline scaffold with excellent in vitro and in vivo anti-CRC activities by targeting Hsp90 to disturb Wnt/β-catenin signaling pathway, which lay a foundation for discovering more effective CRC-targeted therapies.

P2, N=26, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

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

Eribulin was administered, but due to the patient's inability to tolerate the treatment, she passed away 3 months after rectal lesion diagnosis. Although breast cancer metastasis to the rectum is rare, clinicians should consider the possibility of rectal involvement and perform a digital rectal examination if anal symptoms are present.

Eribulin response in MBC can be driven by clinical and biological factors. Application of our nomogram could assist in the prescription of eribulin.

In the TNBC cells, AQP5 modulates the expression levels of EMT-related proteins through activation of Wnt/β-catenin signaling pathway, thus enhancing the cell proliferation, migration and invasion while inhibiting the cell apoptosis.

Since approval, there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types, including hormone receptor positive, HER2 positive and triple negative breast cancer, many demonstrating promising activity. This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent, its toxicity profile, and potential future directions.

In conclusion, our findings suggest that combined application of ICG-001 and anti-PD-1 antibody exhibits significantly enhanced antitumor efficacy. Hence, combining a WNT/β-catenin signaling pathway inhibitor with anti-PD-1 therapy may be a promising treatment strategy for patients with HCC.

P1/2, N=89, Active, not recruiting, Eisai Inc. | Trial completion date: Sep 2025 --> Nov 2024 | Trial primary completion date: Sep 2025 --> Nov 2024

Doxorubicin, eribulin, and pazopanib were administered, but the disease progressed with each drug, and she died. Both of the cases we experienced were women in their 40s, and it took a certain amount of time before the diagnosis of malignancy was made. We report this case with a literature review

Eribulin and pazopanib were administered, but the treatment was ineffective and the patient passed away...The patient requested conservative observation with only denosumab administration, and subsequently passed away...These two mutations were consistent with Cowden syndrome and Li-Fraumeni syndrome, but there was no family history, so the patient was diagnosed with a somatic mutation. We report the progress of the cases and the genetic mutations, including a literature review

After that, she was treated with ①ANA (combined with Demosmab), ②fulvestrant, ③TS-1, ④Capecitabine, and transferred to our hospital at her own request. At the time of transfer, multiple liver metastases were found, and treatment was continued with ⑤abemaciclib+FUL, ⑥PTX+BEV, and ⑦eribulin...⑩Treatment with CPT-11 resulted in PD, and the patient passed away after developing BSC. &lsqb;Discussion] In the former gBRCA2 mutation, a mutant protein is produced in which the latter 45% of the BRCA2 molecule, including the DNA binding domain, is shortened, while in the latter sBRCA2 mutation, a deletion that slightly shortens the RAD51 binding site, producing a mutant protein that is only shortened by 3.6% of the total. Although there have been no reports of molecular function analysis specific to this mutation, it is possible that the former mutation may have partially restored function, which may have contributed to the mechanism of primary resistance to olapalib

Paclitaxel induces multipolar spindles at clinically relevant doses but does not substantially increase mitotic indices...Eribulin and vinorelbine have also been reported to cause increases in multipolar spindles in cancer cells...In genomically stable healthy human cells, delayed anaphase entry may suppress the level of multipolar spindles induced by anti-cancer drugs and lower mitotic cytotoxicity. We outline specific combinations of molecules to investigate that may achieve the goal of enhancing the effectiveness of anti-cancer agents.

The therapeutic potential of targeting the β-catenin/CBP interaction has been demonstrated in a variety of preclinical tumor models with a small molecule inhibitor, ICG-001, characterized as a β-catenin/CBP antagonist...We finally elicit the deletion of a looping of IRS1-a key insulin signaling gene-significantly impeding pancreatic cancer cell growth, indicating that looping-mediated insulin signaling might act as an oncogenic pathway to promote pancreatic cancer progression. Our work shows that targeting aberrant insulin chromatin looping in pancreatic cancer might provide a therapeutic benefit.

The possible interaction between DD-9 and β-catenin and GSK3-β protein was further confirmed by molecular docking studies. Collectively, DD-9 may suppress proliferation and induce apoptosis of liver and cervical cancer cells, possibly at least in part via GSK3-β-mediated crosstalk with the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of DD-9 on hepatocellular and cervical cancer.