Abstract 1829
Background
Eribulin is one of the well-tolerated microtubule dynamics inhibitor made in Japan, and it has been reported to be especially effective for triple negative breast cancer (TNBC) with poor prognosis. We previously reported the possibility of the combination treatment of eribulin and a novel HDAC inhibitor OBP-801 for the promising strategy against TNBC patients. We also interestingly showed that the combination more potently suppressed a MAPK pathway than each agent. Therefore, in this study we investigated the effect of new combination therapy, eribulin and a RAF/MEK inhibitor in TNBC.
Methods
We used CH5126766 as a novel RAF/MEK inhibitor. The phase I clinical trial of CH5126766 is now in progress in the U.S. We investigated the combination effect of eribulin and CH5126766 using some TNBC cell lines. The cell growth was analyzed through WST-8 assay and colony formation assay, and the flow cytometry analysis was conducted to evaluate the induction of apoptosis. The mechanism underlying the enhancement of inhibition of TNBC growth was investigated through Western blot analyses. We also analyzed the combination effect through the onco-immunological mechanism.
Results
The combination treatment showed the inhibition of the TNBC cell growth in both short and long incubation. The mechanism of this combination is due to the enhancement of apoptosis. The apoptosis in the combination was induced with the suppression of anti-apoptotic protein survivin in the TNBC cells. Though eribulin upregulated survivin, CH5126766 could potently suppress the survivin expression induced by eribulin. On the other hand, eribulin could suppress the Akt pathway induced as the result of the resistance of the MAPK pathway. Moreover, CH5126766 might be effective in this combination through the onco-immunological mechanism.
Conclusions
We found that the combination of eribulin and CH5126766 inhibits the growth with apoptosis in TNBC, raising the possibility that the combination might be a novel promising strategy for patients suffering from TNBC with the upregulation of MAPK pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T. Sakai: Research grant / Funding (institution), Licensing / Royalties: Chugai. All other authors have declared no conflicts of interest.
Resources from the same session
3290 - Identification of meningioma patients in high risk of tumor recurrence using microRNA profiling
Presenter: Josef Srovnal
Session: Poster Display session 3
Resources:
Abstract
2477 - Antecedent of cancer and mortality after the first ST segment elevation acute myocardial infarction treated with primary coronary angioplasty. A prospective cohort study
Presenter: Irene Sillero
Session: Poster Display session 3
Resources:
Abstract
1894 - Genomic characterisation of locally advanced pancreatic adenocarcinoma
Presenter: Sarah Picardo
Session: Poster Display session 3
Resources:
Abstract
3280 - Comparison of freshly prepared and frozen cells from colorectal cancer surgical samples for phenotyping experiments- a pilot study
Presenter: Sandra Mersakova
Session: Poster Display session 3
Resources:
Abstract
3419 - Hyaluronan (HA) Accumulation in the Tumor Microenvironment (TME) is Increased in Colorectal Cancer (CRC) and Associated with Consensus Molecular Subtypes (CMS) 4 Molecular Subtype
Presenter: Barbara Blouw
Session: Poster Display session 3
Resources:
Abstract
1833 - Evaluation of CT-based radiomics in patients with renal cell carcinoma
Presenter: An Zhao
Session: Poster Display session 3
Resources:
Abstract
5883 - Detection of Double Protein Expression in Diffuse Large B Cell Lymphoma
Presenter: Mohamed Gouda
Session: Poster Display session 3
Resources:
Abstract
5415 - Encyclopedic Tumor Analysis for organ agnostic treatment with Axitinib in combination regimens for advanced cancers
Presenter: Tim Crook
Session: Poster Display session 3
Resources:
Abstract
3297 - Computational model to predict response rate of clinical trials
Presenter: Orsolya Lorincz
Session: Poster Display session 3
Resources:
Abstract
4355 - Analysis of BRCA genes and homologous recombination deficiency (HRD) scores in tumours from patients (pts) with metastatic breast cancer (mBC) in the OlympiAD trial
Presenter: Mark Robson
Session: Poster Display session 3
Resources:
Abstract