With its distinct binding profile, HALAVEN causes irreversible mitotic blockage resulting in apoptosis, leading to the destruction of many tumor cells.2-5
*Preclinical evidence does not imply clinical efficacy.
HALAVEN binds with high affinity to the growing plus ends of microtubules.6
Microtubule growth occurs primarily at these plus ends4
HALAVEN sequesters tubulin into nonproductive aggregates, preventing participation in microtubule assembly.2,4,5
Microtubules are a key part of the cell-division process, allowing tumor growth7
HALAVEN inhibits microtubule growth and prevents normal mitotic spindle formation.2,4
Disruption of microtubule function results in mitotic blockage, leading to tumor cell death by apoptosis4
HALAVEN induces apoptosis and may impact the residual tumor cells2,8
By promoting the epithelial phenotype, HALAVEN reduces the migration and invasive capacity of tumor cells.2,8,9
*Preclinical evidence does not imply clinical efficacy.
†Based on preclinical studies, including human breast cancer models (in vitro/in vivo).
HALAVEN induces vascular remodeling, increasing oxygen flow to the tumor.2,9
Abnormal vasculature causes irregular blood flow throughout the tumor, resulting in hypoxic regions10
HALAVEN reduces the hypoxic conditions associated with an abnormal tumor microenvironment.2,9
Hypoxic conditions lead to phenotypic changes that cause increased migration and invasive capacity of the tumor cells10,11
HALAVEN opposes the mesenchymal phenotype and promotes the epithelial phenotype.2,8
The mesenchymal phenotype correlates with increased migration and invasiveness of tumor cells8
HALAVEN makes residual tumor cells into ones that are less prone to migrate and invade2
References: 1. Towle MJ, Salvato KA, Budrow J, et al. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001;61(3):1013-1021. 2. HALAVEN [package insert]. Nutley, NJ: Eisai Inc. 3. Towle MJ, Salvato KA, Wels BF, et al. Eribulin induces irreversible mitotic blockade: implications of cell-based pharmacodynamics for in vivo efficacy under intermittent dosing conditions. Cancer Res. 2011;71(2):496-505. 4. Jordan MA, Kamath K, Manna T, et al. The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther. 2005;4(7):1086-1095. 5. Kuznetsov G, Towle MJ, Cheng H, et al. Induction of morphological and biochemical apoptosis following prolonged mitotic blockage by halichondrin B macrocyclic ketone analog E7389. Cancer Res. 2004;64(16):5760-5766. 6. Smith JA, Wilson L, Azarenko O, et al. Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry. 2010;49(6):1331-1337. 7. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4(4):253-265. 8. Yoshida T, Ozawa Y, Kimura T, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states. Br J Cancer. 2014;110(6):1497-1505. 9. Funahashi Y, Okamoto K, Adachi Y, et al. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. Cancer Sci. 2014;105(10):1334-1342. 10. Dybdal-Hargreaves NF, Risinger AL, Mooberry SL. Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res. 2015;21(11):2445-2452. 11. Jiang J, Tang YL, Liang XH. EMT: a new vision of hypoxia promoting cancer progression. Cancer Biol Ther. 2011;11(8):714-723.