-
Breast Cancer (Dove Medical Press) 2021Eribulin mesylate, a synthetic derivative of the anti-mitotic agent halichondrin B, has a unique tubulin-based mechanism of action that is distinct from other... (Review)
Review
Eribulin mesylate, a synthetic derivative of the anti-mitotic agent halichondrin B, has a unique tubulin-based mechanism of action that is distinct from other anti-microtubule agents including taxanes and vinca alkaloids. Consistent with this unique activity, eribulin has shown clinical efficacy in patients with metastatic breast cancer (MBC) that progressed following prior taxane and anthracycline therapy. The evidence presented in this review indicates that eribulin represents a treatment option for patients with HER2-negative metastatic breast cancer. Improved survival outcomes and better tolerability compared with vinorelbine supported the first approval of eribulin in China in 2019; eribulin was approved for women with locally advanced/metastatic HER2-negative breast cancer after treatment failure with at least two chemotherapy regimens, including an anthracycline and a taxane. Eribulin has also shown promising efficacy in patients with HER2-positive advanced breast cancer when used in combination with trastuzumab or pertuzumab, and subgroup analyses from the Phase III clinical trials support the continued evaluation of eribulin in patients with triple-negative disease. The unique non-mitotic effects of eribulin, including vascular remodeling, coupled with its clinical efficacy and safety profile, may permit the broader use of this agent in patients with MBC.
PubMed: 33658845
DOI: 10.2147/BCTT.S231298 -
Cancers Jun 2021Extracellular vesicles play a central role in intercellular communication and contribute to cancer progression, including the epithelial-to-mesenchymal transition (EMT)....
Extracellular vesicles play a central role in intercellular communication and contribute to cancer progression, including the epithelial-to-mesenchymal transition (EMT). Microtubule targeting agents (MTAs) including eribulin and paclitaxel continue to provide significant value in cancer therapy and their abilities to inhibit oncogenic signaling pathways, including eribulin's capacity to reverse EMT are being revealed. Because microtubules are involved in the intracellular trafficking required for the formation and cargo loading of small extracellular vesicles (sEVs), we investigated whether MTA-mediated disruption of microtubule-dependent transport would impact sEV release and their cargo. Eribulin and paclitaxel caused an intracellular accumulation of CD63, a tetraspanin component of sEVs, in late/multivesicular endosomes of triple-negative breast cancer cells, consistent with the disruption of endosomal sorting and exosome cargo loading in these cells. While the concentrations of sEVs released from MTA-treated cells were not significantly altered, levels of CD63 and the CD63-associated cargos, ILK and β-integrin, were reduced in sEVs isolated from eribulin-treated HCC1937 cells as compared to vehicle or paclitaxel-treated cells. These results show that eribulin can reduce specific sEV cargos, including ILK, a major transducer of EMT in the tumor microenvironment, which may contribute to eribulin's ability to reverse EMT to promote anticancer efficacy.
PubMed: 34205051
DOI: 10.3390/cancers13112783 -
Cancers Dec 2022Despite the advances in understanding the biology of hematologic neoplasms which has resulted in the approval of new drugs, the therapeutic options are still scarce for...
Despite the advances in understanding the biology of hematologic neoplasms which has resulted in the approval of new drugs, the therapeutic options are still scarce for relapsed/refractory patients. Eribulin is a unique microtubule inhibitor that is currently being used in the therapy for metastatic breast cancer and soft tissue tumors. Here, we uncover eribulin's cellular and molecular effects in a molecularly heterogeneous panel of hematologic neoplasms. Eribulin reduced cell viability and clonogenicity and promoted apoptosis and cell cycle arrest. The minimal effects of eribulin observed in the normal leukocytes suggested selectivity for malignant blood cells. In the molecular scenario, eribulin induces DNA damage and apoptosis markers. The , , p-AKT, p-NFκB, and NFκB levels were associated with responsiveness to eribulin in blood cancer cells, and a resistance eribulin-related target score was constructed. Combining eribulin with elacridar (a P-glycoprotein inhibitor), but not with PDTC (an NFkB inhibitor), increases eribulin-induced apoptosis in leukemia cells. In conclusion, our data indicate that eribulin leads to mitotic catastrophe and cell death in blood cancer cells. The expression and activation of MDR1, PI3K/AKT, and the NFκB-related targets may be biomarkers of the eribulin response, and the combined treatment of eribulin and elacridar may overcome drug resistance in these diseases.
PubMed: 36551566
DOI: 10.3390/cancers14246080 -
Journal of Geriatric Oncology Jul 2020Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting.
METHODS
We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described.
RESULTS
The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%).
CONCLUSIONS
This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.
Topics: Aged; Breast Neoplasms; Furans; Humans; Ketones; Retrospective Studies; Treatment Outcome
PubMed: 32299685
DOI: 10.1016/j.jgo.2020.03.021 -
Frontiers in Oncology 2017Liposarcoma is one of the most common subtypes of soft-tissue sarcoma and consists of three main subtypes, of which well-differentiated liposarcoma and dedifferentiated... (Review)
Review
Liposarcoma is one of the most common subtypes of soft-tissue sarcoma and consists of three main subtypes, of which well-differentiated liposarcoma and dedifferentiated liposarcoma account for 40-45%. The current mainstay of systemic treatment for patients with metastatic or unresectable disease remains doxorubicin with or without ifosfamide in the first-line setting. Recently, eribulin and trabectedin have been approved by the US Food and Drug Administration for recurrent liposarcomas and progress in molecular characterization of these tumors has opened up new and potential novel treatment targets. This review will focus on the evidence base for current treatment strategies and will also discuss potential future options.
PubMed: 29250486
DOI: 10.3389/fonc.2017.00292 -
Frontiers in Pharmacology 2022Systemic chemotherapy for advanced disease is another therapeutic option in the management of metastases in soft tissue sarcoma (STS). Doxorubicin either alone or in... (Review)
Review
Systemic chemotherapy for advanced disease is another therapeutic option in the management of metastases in soft tissue sarcoma (STS). Doxorubicin either alone or in combination with ifosfamide has been used as first-line chemotherapy. Furthermore, in the past decade, new drugs have been shown to be effective in the treatment of advanced STS after the failure of first-line anthracycline-based chemotherapy: trabectedin, pazopanib and eribulin. However, the appropriate usage of these agents has not been established. We summarized clinical trials of trabectedin focusing on the efficacy and toxicity of trabectedin in the treatment of STS. Trabectedin can be administered safely and effectively to the patients with advanced STS at second line setting or later. Although trabectedin may be effective as first-line treatment in selected patients, anthracycline-based chemotherapy should be recommended because no regimen in addition to trabectedin has proved to be unequivocally superior to doxorubicin as the first-line treatment for locally advanced or metastatic STS. Nucleotide excision repair (NER) and homologous recombination (HRe) repair may be of particular importance as efficacy of trabectedin. Trabectedin has shown a favorable toxicity profile and is an alternative therapeutic option in patients with advanced STS.
PubMed: 35281940
DOI: 10.3389/fphar.2022.777872 -
Oral Oncology Jan 2024Salivary gland cancers (SGCs) are a heterogeneous group of rare tumors including various histological subtypes with different molecular profiling. Human epidermal growth... (Review)
Review
Salivary gland cancers (SGCs) are a heterogeneous group of rare tumors including various histological subtypes with different molecular profiling. Human epidermal growth factor receptor 2 (HER2) is one of the most intriguing and studied molecular alterations with prognostic and predictive roles. Indeed, HER2 overexpression is commonly correlated with aggressive histological subtypes and poorer prognosis. However, HER2 may represent the target of personalized treatment. We performed a literature review of use of anti-HER2 targeted agents for treatment of recurrent or metastatic SGCs. The efficacy and safety of anti-HER2 were firstly evaluated in patients affected with other solid tumors, mostly breast and gastric cancers. For SGCs the literature is mainly comprised of case reports or case series and small clinical trials. The most common used drug is trastuzumab in combination with chemotherapy (i.e. taxanes, capecitabine, carboplatin, eribulin) or with another anti-HER2 targeted agent (i.e. pertuzumab). The use of anti-HER2 therapies induces improvement in clinical responses, which are mostly durable. Besides, new anti-HER2 drugs such as antibody-drug conjugates (ADC) (i.e. trastuzumab emtansine, trastuzumab deruxtecan) have been introduced in this setting inducing further therapeutic advances. Anti-HER2 treatment strategy is emerging as potentially effective in selected HER2 overexpressing SGCs. However, prospective and multicentric clinical trials are needed to evaluate the efficacy of these therapeutic regimens within larger cohorts and to assess the most appropriate treatment sequence strategy.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Carboplatin; Prospective Studies; Salivary Gland Neoplasms
PubMed: 38016228
DOI: 10.1016/j.oraloncology.2023.106612 -
Critical Reviews in Oncology/hematology Feb 2012Eribulin mesylate is a non-taxane, structurally simplified, completely synthetic, halichondrin B derivative with an end poisoning, microtubule inhibitory action.... (Review)
Review
Eribulin mesylate is a non-taxane, structurally simplified, completely synthetic, halichondrin B derivative with an end poisoning, microtubule inhibitory action. Preclinical studies have demonstrated activity in various cancer cell lines and synergistic action with gemcitabine, epirubicin, trastuzumab, cisplatin, docetaxel and vinorelbine. Eribulin has recently been approved by United States Food and Drug Administration as a third line therapy for metastatic breast cancer patients, who have previously been treated with an anthracycline and a taxane. It has also advanced to phase II trials in non-small cell lung cancer, pancreatic, prostate, bladder, head and neck cancers, sarcomas and ovarian and other gynecological tumors. Combination trials with carboplatin, gemcitabine, pemetrexed, cisplatin, and erlotinib are currently ongoing. Eribulin potentially has a low incidence of peripheral neuropathy. The predominant side effects are neutropenia and fatigue, which are manageable. This article reviews the available information on eribulin with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, preclinical studies and clinical trials.
Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Furans; Humans; Ketones; Neoplasms
PubMed: 21493087
DOI: 10.1016/j.critrevonc.2011.03.002 -
Frontiers in Bioscience (Scholar... Dec 2021Eribulin, a synthetic marine based drug has received extensive attention recently due to its promising anticancer activities against a wide variety of cancer types as... (Review)
Review
Eribulin, a synthetic marine based drug has received extensive attention recently due to its promising anticancer activities against a wide variety of cancer types as evidenced by preclinical and clinical data. Eribulin is predominantly shown to exhibit microtubule inhibitory activity, however recent reports indicate that it acts via multiple molecular mechanisms targeting both the cancer cells as well as the tumor microenvironment. In this review, a comprehensive account on various modes of action of eribulin on cancer cells is presented along with important clinical aspects in the management of cancer through a comprehensive literature review. We have also highlighted approaches including combination therapy to improve the efficacy of eribulin in cancer treatment. Currently, eribulin is used to treat heavily pretreated patients with metastatic breast cancer, for which it gained FDA approval a decade ago and more recently, it has been approved for treating anthracycline-pretreated patients with metastatic liposarcoma. Novel therapeutic strategies should aim at resolving the toxicity and resistance conferred due to eribulin treatment so that it could be integrated in the clinics as a first-line treatment approach.
Topics: Antineoplastic Agents; Breast Neoplasms; Female; Furans; Humans; Ketones; Microtubules; Tumor Microenvironment
PubMed: 34879468
DOI: 10.52586/S559 -
Medicina (Kaunas, Lithuania) Apr 2022; Triple-negative breast cancer (TNBC) is associated with poor patient prognosis because of its multiple molecular features. Thus, more effective treatment for TNBC is...
; Triple-negative breast cancer (TNBC) is associated with poor patient prognosis because of its multiple molecular features. Thus, more effective treatment for TNBC is urgently needed. This study determined the possible involvement of ERK1/2 activation in cisplatin-induced cytotoxicity in TNBC by providing additional eribulin treatment. ; We investigated cell viability and apoptosis caused by eribulin, cisplatin, or co-treatment in HCC38, MDA-MB-231, and SKBR3 human breast cancer cells. ; Cisplatin significantly lowered cell viability and caused high apoptotic cell death in all breast cancer cell lines. The viability of TNBC cells was significantly lower in the group co-treated with cisplatin and eribulin than in the cisplatin-only treatment group. Additional eribulin treatment significantly enhanced PARP cleavage and caspase-3 activity in cisplatin-treated TNBC cells. Moreover, cisplatin treatment activated ERK1/2 in all breast cancer cell lines. The cisplatin and eribulin combination synergistically activated ERK1/2 in TNBC cells compared with the cisplatin-only treatment. Administration of the ERK1/2 inhibitor PD98059 increased the viability of TNBC cells treated with cisplatin plus eribulin. ; Eribulin could synergize the cytotoxic and apoptotic activities of cisplatin and increase ERK1/2 activation, thus enhancing anti-cancer effects against TNBC cells.
Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cisplatin; Furans; Humans; Ketones; Mitogen-Activated Protein Kinase 3; Triple Negative Breast Neoplasms
PubMed: 35454385
DOI: 10.3390/medicina58040547