Cancer is a genetic disease with increasing heterogeneity during disease progression. However, despite the widespread use of genomic testing, a recent publication estimated that only 5% of cancer patients in the US benefit from genome-driven targeted therapies, largely because “actionable mutations” are rare.[1] Thus, SageMedic has developed the SAGE Direct Test™, leading the next generation of functional precision medicine to accurately predict the most effective treatment for virtually all cancer patients without limitations of genomic sequencing or having to identify a specific pathway. Our SAGE Direct Test™ consists of four critical steps, i.e., tissue processing, creation of 3D microtumors, live/dead cell imaging, and metabolic profiling. Using our proprietary technology, we can create hundreds of 3D microtumors from a core needle biopsy sample that recapitulate the in vivo tumor heterogeneity and microenvironment of the tumor biopsy. After these microtumors have been treated with a panel of drugs, we quantify the number of live and dead cells in those microtumors using our proprietary technology and scalable automatic stage confocal imaging (Molecular Devices). The advantage of our SAGE Direct Platform™ is the ability to multiplex our image-based results with the metabolic profile of our 3D microtumors, which cross validates our image-based readout. Our SAGE Direct Test™ has been optimized with ATCC cell lines and further validated with patient-derived tumor cells from lung, ovarian, and colon cancer tumor samples. Validation of high-quality confocal imaging samples followed by quantitative metabolic analysis suggests accurate quantification of viable cells, as reflected in a positive correlation between imaging quantitation and metabolic analysis (correlation coefficient r=0.84, p<0.01). In summary, SageMedic has developed the SAGE Direct Test™, a simple, highly sensitive, robust, and straightforward functional profiling assay with significant clinical relevance, as it can model the natural physiological conditions of tumors.

[1] Marquart et al. Estimation of the Percentage of US Patients With Cancer Who Benefit From Genome-Driven Oncology. JAMA Oncology 2018 Aug 1;4(8):1093-1098

Citation Format: Dhruva Mishra, Jennifer Moy, Chris Apfel. The SAGE Direct TestTM: A reliable way of functional profiling to predict the most effective treatment for cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5255.