Abstract A036: Identification of secretome-based eribulin biomarkers for breast cancer therapeutics
Authors: Bellio Chiara , Duran Juan M. , Méndez Olga , Meo-Evoli Nathalie , Salvans Cándida , Garrigós Laia , Zamora Esther , Saura Cristina , Littlefield Bruce A , Villanueva Josep 
Published: March 2020

Microtubules are major components of the cytoskeleton. They are involved in a wide variety of cell functions including attribution to cell shape, motility, intracellular trafficking and mitotic spindle formation. Therefore, microtubules have gained significant interest as important targets for cancer therapy. Several microtubule-targeting agents (MTAs) are being used to treat cancer patients. Eribulin is a novel microtubule dynamic inhibitor approved for treatment of metastatic breast cancer (MBC) after two previous lines of therapy and the only cytotoxic agent in recent years to improve overall survival (OS) in heavily pretreated patients. A challenge for achieving successful management of cancer is the discovery of tumor biomarkers that represent useful surrogates during the course of the disease and therapeutic treatment, and that can be measured non-invasively. Over the last few years there has been an increasing interest in the study of cancer secretome, a sub-proteome that contains secreted and shed plasma membrane proteins. The rationale supporting this approach is that secretomes have a much lower complexity than plasma and tissue homogenates, and may be enriched with proteins that are very likely to enter the circulation. The presence of proteins linked to cancer such as growth factors and proteases in these fluids indicates that secretomes might help in monitoring critical aspects of cancer progression and therapeutic treatment. The working hypothesis for this study is that there is a secretome induced by eribulin that can be measured by quantitative proteomics, and can be used to identify response biomarkers linked to the action of the drug. We used three cell line models representing triple negative breast cancer (TNBC), MDA-MB-231 and MX1, and luminal BC, MCF7, which were already proven to be sensitive to eribulin. We generated secretomes by quantitative proteomics from these cell lines during the treatment with eribulin, and we compared them to the control secretomes from the same cell lines. The statistical analysis of the data revealed a specific secretome that could reflect the action of eribulin on tumor cells. Specifically, eribulin treatment induced the oversecretion of the same families of protein in the three different BC cell lines. In the near future, we will select candidate biomarkers for validation in samples obtained from metastatic patients at baseline and during treatment, and we will correlate their levels with the standard response evaluation by diagnostic radiologic exams. This project is the collaborative effort between the Tumor Biomarkers laboratory at VHIO, the Breast Cancer Program at Vall d’Hebron Hospital and Eisai. We are confident that identifying the eribulin-based secretome could help monitoring critical aspects of cancer therapeutic MBC treatment.

Citation Format: Chiara Bellio, Juan M. Duran, Olga Méndez, Nathalie Meo-Evoli, Cándida Salvans, Laia Garrigós, Esther Zamora, Cristina Saura, Bruce A Littlefield, Josep Villanueva. Identification of secretome-based eribulin biomarkers for breast cancer therapeutics [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A036. doi:10.1158/1535-7163.TARG-19-A036