clinically formulated mesylate salt form of eribulin as halaven  (Eisai Inc)

Journal: Cancer Research Communications

Article Title: Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models

doi: 10.1158/2767-9764.CRC-24-0047

Figure Lengend Snippet: Tumor growth response to eribulin and copanlisib, either alone or in combination in WHIM29 and WHIM34. A, Tumor volume changes over time compared with that of day 1 after receiving either vehicle, eribulin (0.3 mg/kg i.p. on day 1 of each week × 4, except that 0.1 mg/kg eribulin was administered for the first two doses in WHIM29), copanlisib (10 mg/kg i.v. on days 2 and 3 each week × 4), or the combination of copanlisib and eribulin at the same dosing ( n = 5 per group). B, Kaplan–Meier survival duration (days) of tumor-bearing mice after receiving treatments indicated in A. *, P < 0.05; **, P < 0.01, comparing between groups received eribulin or the combination of eribulin and copanlisib.

Article Snippet: Eribulin mesylate (Halaven, Eisai Inc) is a non-taxane inhibitor of microtubule dynamics that is approved for the treatment of metastatic breast cancers previously treated with anthracycline and taxane ( ).

Techniques:

Journal: Cancer Research Communications

Article Title: Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models

doi: 10.1158/2767-9764.CRC-24-0047

Figure Lengend Snippet: Expression of protein markers significantly altered by treatment with eribulin in combination with copanlisib in all PDX models. A, Expression of RPPA protein markers significantly altered, with FDR-adjusted P value <0.1, comparing treatment with the combination of eribulin and copanlisib versus vehicle are shown for individual tumors from each PDX model at the completion of 3–4 weeks of treatment with either vehicle, eribulin, copanlisib, or eribulin plus copanlisib. Note that WHIM34 and WHIM29 tumors treated with eribulin or eribulin in combination with copanlisib were missing in the analysis due to insufficient quantity of tumors at the completion of treatment. B, Heat map of estimated coefficient for FDR significantly altered markers ( P < 0.1) comparing copanlisib plus eribulin versus vehicle.

Article Snippet: Eribulin mesylate (Halaven, Eisai Inc) is a non-taxane inhibitor of microtubule dynamics that is approved for the treatment of metastatic breast cancers previously treated with anthracycline and taxane ( ).

Techniques: Expressing

Journal: Cancer Research Communications

Article Title: Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models

doi: 10.1158/2767-9764.CRC-24-0047

Figure Lengend Snippet: Apoptotic induction following treatment with eribulin and copanlisib, either alone or in combination by IHC. Representative IHC pictures ( A ) and quantifications of IHC scores ( B ) of cleaved PARP on WHIM29 and WHIM34 PDX tumors harvested on day 3 following treatment with either vehicle (day 1), eribulin (day 1), copanlisib (days 1 and 2), or the combination, and FDG PET 4 hours after treatment on day 2.

Article Snippet: Eribulin mesylate (Halaven, Eisai Inc) is a non-taxane inhibitor of microtubule dynamics that is approved for the treatment of metastatic breast cancers previously treated with anthracycline and taxane ( ).

Techniques:

Journal: Cancer Research Communications

Article Title: Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models

doi: 10.1158/2767-9764.CRC-24-0047

Figure Lengend Snippet: Expression of protein markers significantly altered by treatment with eribulin in combination with copanlisib in three eribulin-resistant models (WHIM3, WHIM4, and WHIM6). Expression of indicated RPPA protein markers are shown. Aurora_pT288_pT232_pT198, and Histone H3_pS10, were significantly upregulated, with FDR-adjusted P value <0.1, at the completion of 3–4 weeks of treatment with the combination of eribulin and copanlisib versus vehicle. Caspase 7 cleaved was upregulated following combination therapy, although did not reach statistical significance.

Article Snippet: Eribulin mesylate (Halaven, Eisai Inc) is a non-taxane inhibitor of microtubule dynamics that is approved for the treatment of metastatic breast cancers previously treated with anthracycline and taxane ( ).

Techniques: Expressing

Journal: Cancer Research Communications

Article Title: Evaluation of Copanlisib in Combination with Eribulin in Triple-negative Breast Cancer Patient-derived Xenograft Models

doi: 10.1158/2767-9764.CRC-24-0047

Figure Lengend Snippet: Treatment induced changes in FDG uptake by PET imaging and in the levels of pAKT by IHC in WHIM29 and WHIM34. Representative images of FDG PET scan of tumor-bearing mice performed pretreatment and posttreatment (on day 2, 4 hours following drug dosing) with either vehicle, copanlisib (10 mg/kg i.v., on day 1, and on day 2), eribulin (0.2 or 0.3 mg/kg i.p., on day 1), or the combination of eribulin and copanlisib for WHIM29 ( A ) and WHIM34 ( B ). Quantification of average SUV by FDG PET scan of tumor-bearing mice performed pretreatment and posttreatment with either copanlisib, eribulin, or the combination of copanlisib and eribulin in WHIM29 ( n = 5; C ) and WHIM34 ( n = 5; D ). ***, P < 0.001; ****, P < 0.0001. Representative IHC images for pAKT473 and cleaved PARP on tumor tissue sections harvested on day 3, following treatment with either vehicle, copanlisib (10 mg/kg i.v., on day 1, and on day 2), eribulin (0.2 or 0.3 mg/kg i.p., on day 1), or the combination of eribulin and copanlisib for WHIM29 ( E ) and WHIM34 ( F ).

Article Snippet: Eribulin mesylate (Halaven, Eisai Inc) is a non-taxane inhibitor of microtubule dynamics that is approved for the treatment of metastatic breast cancers previously treated with anthracycline and taxane ( ).

Techniques: Imaging

Journal: Molecular Cancer Therapeutics

Article Title: Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody

doi: 10.1158/1535-7163.MCT-22-0475

Figure Lengend Snippet: Antitumor activity of eribulin and eribulin-LF in immunodeficient versus immunocompetent mice. A, Antitumor activity of eribulin and eribulin-LF in 4T1#31 subcutaneous transplantation model in immunodeficient and immunocompetent mice. When the average TV reached 80 to 100 mm 3 , tumor-bearing mice were intravenously injected with eribulin (Eri) or eribulin-LF (Eri-LF) at 0.3 mg/kg on a Q7D×2 ( n = 6 per group). Data are presented as mean + SEM. **, P < 0.01 and ****, P < 0.0001 by two-way repeated-measures ANOVA with Tukey multiple-comparisons test using log-transformed values, and statistical results of the difference of TV on the indicated days are shown. B, Comparison of the antitumor activity of eribulin and eribulin-LF in immunodeficient and immunocompetent mice. The ΔT/C value (% of control for Δgrowth) on the last day of measurement was calculated ( n = 6 per group). *, P < 0.05; **, P < 0.01; ***, P < 0.001; and ****, P < 0.0001 by one-way ANOVA with Tukey multiple-comparisons test.

Article Snippet: Eribulin mesylate (eribulin, Halaven) and eribulin-LF were manufactured by Eisai Co., Ltd.

Techniques: Activity Assay, Transplantation Assay, Injection, Transformation Assay, Comparison, Control

Journal: Molecular Cancer Therapeutics

Article Title: Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody

doi: 10.1158/1535-7163.MCT-22-0475

Figure Lengend Snippet: Antitumor activity of eribulin-LF + anti–PD-1 Ab. A, Antitumor activity of eribulin-LF + anti–PD-1 Ab or each monotherapy in the 4T1#31 subcutaneous transplantation model. When the average TV reached 90 to 100 mm 3 , mice bearing 4T1#31 tumors were intravenously injected with eribulin (Eri) or eribulin-LF (Eri-LF) in combination or not with anti–PD-1 Ab (200 μg/mouse) on a Q7D×2 schedule ( n = 6 per group). Data are presented as mean + SEM. *, P < 0.05; **, P < 0.01; ****, P < 0.0001; and ns, not significant by two-way repeated-measures ANOVA with Tukey multiple-comparisons test using log-transformed values, and statistical results of the difference of TV on the indicated days are shown. B, Waterfall plots across five independent experiments. The best overall response was calculated by comparing the TV change on day t with the baseline TV on day 1 for t ≥ 8. The best percentage changes from baseline that exceeded 200% are shown as 200% in the plots. C, Antitumor activity of eribulin-LF + anti–PD-1 Ab in RAG tumors. Mice bearing RAG tumors were treated with 0.3 mg/kg Eri-LF (intravenously) on a Q7D×3 schedule + anti–PD-1 Ab (200 μg/mouse; intraperitoneally) on a Q3D×7 schedule or with each monotherapy ( n = 10 per group). Data are presented as mean + SEM. *, P < 0.05 and ****, P < 0.0001 by two-way repeated-measures ANOVA with Dunnett multiple-comparisons test.

Article Snippet: Eribulin mesylate (eribulin, Halaven) and eribulin-LF were manufactured by Eisai Co., Ltd.

Techniques: Activity Assay, Transplantation Assay, Injection, Transformation Assay

Journal: Molecular Cancer Therapeutics

Article Title: Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody

doi: 10.1158/1535-7163.MCT-22-0475

Figure Lengend Snippet: Effect of eribulin-LF + anti–PD-1 Ab on MVD and TILs. A, Scheme of tumor sampling. When the average TV reached 60 to 120 mm 3 , immunocompetent BALB/c mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin or eribulin-LF + anti–PD-1 Ab (200 μg/mouse) or each monotherapy on day 1 (only 1 injection; intravenously). Tumors were collected on day 8 or day 11 from each mouse and used for the following analyses. FCM, flow cytometry. B and C, Eribulin-LF has superior vascular remodeling activity compared with eribulin. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin (Eri; intravenously) or eribulin-LF (Eri-LF; intravenously). Tumors were collected on day 11, and IHC analysis was performed. B, Representative IHC images showing CD31 staining. Bar, 100 μm. C, MVD in whole tumor tissues was quantified ( n = 7–8 per group). Data are presented as mean ± SEM. *, P < 0.05; **, P < 0.01; and ****, P < 0.0001 by one-way ANOVA with Tukey multiple-comparisons test. D and E, Eribulin-LF has vascular remodeling activity. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin-LF (Eri-LF; intravenously) + anti–PD-1 Ab (200 μg/mouse; intravenously) or each monotherapy. Tumors were collected on day 11, and IHC analysis was performed. D, Representative IHC images showing CD31 staining. Bar, 100 μm. E, MVD in whole tumor tissue was quantified ( n = 8 per group). Data are presented as mean ± SEM. *, P < 0.05 and ***, P < 0.001 by one-way ANOVA with Dunnett multiple-comparisons test. F, Flow cytometric analysis of TILs in 4T1#31 tumors. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin (Eri; intravenously) or eribulin-LF (Eri-LF; intravenously). Tumors were collected on day 11, and TILs from dissociated tumor tissue cells were analyzed by flow cytometric analysis ( n = 8 per group). T cells, CD4 + T cells, CD8 + T cells, and NK cells were gated as CD3 + CD11b − cells, CD4 + CD3 + CD11b − cells, CD8 + CD3 + CD11b − cells, and CD49b + CD3 − cells, respectively. Data are shown as box plots with Tukey-style whiskers. *, P < 0.05; **, P < 0.01; ***, P < 0.001; and ****, P < 0.0001 by one-way ANOVA with Tukey multiple-comparisons test. G, Flow cytometric analysis of TILs in 4T1#31 tumors. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin-LF (Eri-LF; intravenously) + anti–PD-1 Ab (200 μg/mouse; intravenously) or each monotherapy. Tumors were collected on day 11, and flow cytometric analysis of TILs was performed ( n = 11–12 per group). T cells, CD4 + T cells, CD8 + T cells, and NK cells were gated as CD3 + CD11b − cells, CD4 + CD3 + CD11b − cells, CD8 + CD3 + CD11b − cells, and CD49b + CD3 − cells, respectively. GzmB + CD8 + T cells were gated as GzmB + cells in CD8 + T cells. GzmB + NK cells were gated as GzmB + NKp46 + CD49b + cells. Data are shown as box plots with Tukey-style whiskers. *, P < 0.05; **, P < 0.01; ***, P < 0.001; and ****, P < 0.0001 by one-way ANOVA with Dunnett multiple-comparisons test. H and I, Eribulin-LF increased infiltration of CD8 + cells. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin-LF (Eri-LF; intravenously) + anti–PD-1 Ab (200 μg/mouse; intravenously) or each monotherapy. Tumors were collected on day 11 and IHC analysis was performed. H, Representative IHC images showing CD8 staining. Bar, 100 μm. I, CD8 + cell count per unit area of whole tumor tissues was quantified ( n = 8 per group). Data are presented as mean ± SEM. **, P < 0.01 and ***, P < 0.001 by one-way ANOVA with Dunnett multiple-comparisons test.

Article Snippet: Eribulin mesylate (eribulin, Halaven) and eribulin-LF were manufactured by Eisai Co., Ltd.

Techniques: Sampling, Injection, Flow Cytometry, Activity Assay, Staining, Cell Counting

Journal: Molecular Cancer Therapeutics

Article Title: Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody

doi: 10.1158/1535-7163.MCT-22-0475

Figure Lengend Snippet: Effect of eribulin-LF on immune-related gene expression. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin-LF (Eri-LF; intravenously) + anti–PD-1 Ab (200 μg/mouse; intravenously) or each monotherapy ( n = 10 per group). Tumors were collected on day 8, and total RNA was extracted and analyzed by using an nCounter PanCancer Mouse Immune Profiling Panel. A, GSEA. GSEA was performed by using the CERNO algorithm, and P values were calculated by using the CERNO test. We used the immune response category annotations provided by NanoString, and the genes were classified into 30 gene sets based on their annotations. In the figure, the 30 gene-set categories are shown sorted on the basis of the P values for the 0.3 mg/kg Eri-LF group. *, P < 0.05. #adjusted P < 0.05. B, IFNγ signature score was increased by eribulin-LF. IFNγ signature score was calculated using the gene expression data determined by using the nCounter PanCancer Mouse Immune Profiling Panel. Data are presented as mean ± SEM. *, P < 0.05; **, P < 0.01; and ns, not significant by one-way ANOVA with Dunnett multiple-comparisons test.

Article Snippet: Eribulin mesylate (eribulin, Halaven) and eribulin-LF were manufactured by Eisai Co., Ltd.

Techniques: Gene Expression

Journal: Molecular Cancer Therapeutics

Article Title: Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody

doi: 10.1158/1535-7163.MCT-22-0475

Figure Lengend Snippet: Correlation between infiltration of CD8 + cells into tumor and vascular remodeling by eribulin-LF. Representative IHC images of CD8/CD31 double staining. Mice bearing 4T1#31 tumors were treated with 0.3 mg/kg eribulin-LF (Eri-LF; intravenously) + anti–PD-1 Ab (200 μg/mouse; intravenously) or each monotherapy. Tumors were collected on day 11, and IHC analysis was performed. Tissues were stained with anti-CD8α (green) and anti-CD31 (red) Abs, and nuclei were counterstained with DAPI (blue). The dashed line marked “C” indicates the tumor core. Bar, 100 μm.

Article Snippet: Eribulin mesylate (eribulin, Halaven) and eribulin-LF were manufactured by Eisai Co., Ltd.

Techniques: Double Staining, Staining

Journal: Molecular Cancer Therapeutics

Article Title: Liposome-Encapsulated Eribulin Shows Enhanced Antitumor Activity over Eribulin for Combination Therapy with Anti–PD-1 Antibody

doi: 10.1158/1535-7163.MCT-22-0475

Figure Lengend Snippet: Effect of eribulin-LF on expression of ICAM-1 in vascular ECs. Eribulin-LF induced ICAM-1 expression in vascular ECs in 4T1#31 tumors. Mice bearing 4T1#31 tumors were treated with the indicated dose of eribulin-LF (Eri-LF; intravenously). Tumors were collected on day 8, and CD31 + vascular ECs were enriched by magnetic-activated cell sorting. After enrichment of CD31 + vascular ECs, the expression level of ICAM-1 on vascular ECs was evaluated by flow cytometric analysis. A, Representative dot plots (CD45 vs. CD31). Cell suspensions obtained from tumor tissues (before enrichment) and EC-enriched cell suspensions after magnetic-activated cell sorting (after enrichment) were analyzed by flow cytometric analysis. Vascular ECs were gated as CD31 + CD45 − cells (blue lines). B, Representative histogram of ICAM-1 expression in the population gated on CD31 + vascular ECs. The gray line represents the isotype control; and the black, blue, and red lines represent ICAM-1 in the nontreatment, 0.3 mg/kg Eri-LF, and 1.0 mg/kg Eri-LF groups, respectively. C, Mean fluorescence intensities ( n = 5 per group). Data are presented as mean ± SEM. ***, P < 0.001 and ****, P < 0.0001 by one-way ANOVA with Dunnett multiple-comparisons test.

Article Snippet: Eribulin mesylate (eribulin, Halaven) and eribulin-LF were manufactured by Eisai Co., Ltd.

Techniques: Expressing, FACS, Control, Fluorescence

Journal: Marine Drugs

Article Title: Recent Advancement in Anticancer Compounds from Marine Organisms: Approval, Use and Bioinformatic Approaches to Predict New Targets

doi: 10.3390/md21010024

Figure Lengend Snippet: Drugs approved as anticancer compounds obtained from marine sponges: details about sponge species, kind of compound and targets in cancer cells.

Article Snippet: Eribulin mesylate (E7389, Halaven ® , Eisai Inc., under license from Eisai R&D Management Co., Ltd. © 2022 Eisai Inc. HALA-US3824; Cambridge, MA, USA, us.eisai.com , accessed on 23 October 2022) is the simplified synthetic analog of halichondrin B, a molecule isolated for the first time from the marine sponge Halichondria okadai belonging to the Demospongiae class and known for the production of okadaic acid [ ].

Techniques: