Metastatic cancers are difficult to treat and are the cause of about 90% of cancer related deaths. Furthermore, predictive diagnostics are not readily available, and lack of good translational assays has impaired drug discovery. Mestastop has developed a platform of cell based functional assays that aims to address these drug discovery and diagnostic gaps. The platform is comprised of a set of 14 cell based phenotypic assays that capture multiple aspects of the complex process of metastasis, including characterization of the plasticity ratios (EMT, MET) and stemness of cells, invasion, intravasation, circulation, extravasation, and survival in secondary tissues (e.g metabolic shift, exosome secretion). Wild type tumor cells (initially a set of colon tumor cell lines) are utilized in the platform. Non-metastatic wild type cells (e.g. HT-29) that have been engineered into metastatic cells are also utilized to further elucidate metastatic processes, thereby creating two baseline data sets for each assay; one for the normal growing tumor and the other for the select metastatic population. Patient derived tumors are now being analyzed in the platform to help build a translational model. Preclinical animal models are being jointly developed with Immunobiome Inc. (South Korea). As the data from all these assays present a multivariate problem, we are developing a machine learning algorithm, METSCANTM, to analyze the results. The platform will be applied to the screening of novel compounds for drug discovery and of approved drugs for repurposing. Analysis of patient derived tumors may allow for the early detection of patients with high metastatic potential. Four colon cancer cell lines and several standard chemotherapy drugs have been used to validate the platform. A group of triple negative breast cancer cell lines is now being tested. Preliminary data for a set of approved, marketed drugs has further validated the potential of the platform for drug discovery and repurposing. The Mestastop proprietary assay platform will empower biopharma in the discovery of novel drug candidates and repurposing of approved drugs for the treatment of metastasis, and the early diagnosis of cancers with high metastatic potential, thereby addressing the unmet need in the area of cancer metastasis.
Citation Format: Arnab Roy Chowdhury, Debabani Roy Chowdhury, Manoj Pandre, Samrat Roy, Sundarajan Kannan, John W. Ellingboe. A cell based phenotypic assay platform for cancer metastasis drug discovery and diagnostics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2868.