Abstract 822: OncoLoop: Closing the loop between patient-centered drug discovery and preclinical testing in precision-oncology

Author(s):  
Alessandro Vasciaveo ◽  
Min Zou ◽  
Juan Arriaga ◽  
Andrea Califano ◽  
Cory Abate-Shen
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3076-3076
Author(s):  
Shengli Ding ◽  
Zhaohui Wang ◽  
Marcos Negrete Obando ◽  
Grecia rivera Palomino ◽  
Tomer Rotstein ◽  
...  

3076 Background: Preclinical models that can recapitulate patients’ intra-tumoral heterogeneity and microenvironment are crucial for tumor biology research and drug discovery. In particular, the ability to retain immune and other stromal cells in the microenvironment is vital for the development of immuno-oncology assays. However, current patient-derived organoid (PDO) models are largely devoid of immune components. Methods: We first developed an automated microfluidic and membrane platform that can generate tens of thousands of micro-organospheres from resected or biopsied clinical tumor specimens within an hour. We next characterized growth rate and drug response of micro-organospheres. Finally, extensive single-cell RNA-seq profiling were performed on both micro-organospheres and original tumor samples from lung, ovarian, kidney, and breast cancer patients. Results: Micro-organospheres derived from clinical tumor samples preserved all original tumor and stromal cells, including fibroblasts and all immune cell types. Single-cell analysis revealed that unsupervised clustering of tumor and non-tumor cells were identical between original tumors and the derived micro-organospheres. Quantification showed similar cell composition and percentages for all cell types and also preserved functional intra-tumoral heterogeneity.. An automated, end-to-end, high-throughput drug screening pipeline demonstrated that matched peripheral blood mononuclear cells (PBMCs) from the same patient added to micro-organospheres can be used to assess the efficacy of immunotherapy moieties. Conclusions: Micro-organospheres are a rapid and scalable platform to preserve patient tumor microenvironment and heterogeneity. This platform will be useful for precision oncology, drug discovery, and immunotherapy development. Funding sources: NIH U01 CA217514, U01 CA214300, Duke Woo Center for Big Data and Precision Health


Episteme ◽  
2013 ◽  
Vol 10 (4) ◽  
pp. 417-439
Author(s):  
Alexandra Bradner

AbstractDrug discovery traditionally has occurred behind closed doors in for-profit corporations hoping to develop best-selling medicines that recoup initial research investment, sustain marketing infrastructures, and pass on healthy returns to shareholders. Only corporate Pharma has the man- and purchasing-power to synthesize the thousands of molecules needed to find a new drug and to conduct the clinical trials that will make the drug legal. Against this view, individual physician-scientists have suggested that the promise of applied genomics work calls for a new form of social organization – the open source sharing of molecular probes – in order to speed the generation and understanding of new therapeutics. Recent successes in open source drug discovery show it is possible to produce valuable, empirically adequate, and sustainable collective beliefs without secrecy, proprietary attitudes, initial cooperation from Pharma, or outsized monetary incentives. After reviewing and differentiating these successes, I diagnose the source of this healthy new epistemic strategy.


2021 ◽  
Vol 23 (4) ◽  
Author(s):  
Nadia Terranova ◽  
Karthik Venkatakrishnan ◽  
Lisa J. Benincosa

AbstractThe exponential increase in our ability to harness multi-dimensional biological and clinical data from experimental to real-world settings has transformed pharmaceutical research and development in recent years, with increasing applications of artificial intelligence (AI) and machine learning (ML). Patient-centered iterative forward and reverse translation is at the heart of precision medicine discovery and development across the continuum from target validation to optimization of pharmacotherapy. Integration of advanced analytics into the practice of Translational Medicine is now a fundamental enabler to fully exploit information contained in diverse sources of big data sets such as “omics” data, as illustrated by deep characterizations of the genome, transcriptome, proteome, metabolome, microbiome, and exposome. In this commentary, we provide an overview of ML applications in drug discovery and development, aligned with the three strategic pillars of Translational Medicine (target, patient, dose) and offer perspectives on their potential to transform the science and practice of the discipline. Opportunities for integrating ML approaches into the discipline of Pharmacometrics are discussed and will revolutionize the practice of model-informed drug discovery and development. Finally, we posit that joint efforts of Clinical Pharmacology, Bioinformatics, and Biomarker Technology experts are vital in cross-functional team settings to realize the promise of AI/ML-enabled Translational and Precision Medicine.


2016 ◽  
Vol 8 ◽  
pp. BIC.S37548 ◽  
Author(s):  
Louis D. Fiore ◽  
Mary T. Brophy ◽  
Sara Turek ◽  
Valmeek Kudesia ◽  
Nithya Ramnath ◽  
...  

The Department of Veterans Affairs (VA) recognized the need to balance patient-centered care with responsible creation of generalizable knowledge on the effectiveness of molecular medicine tools. Embracing the principles of the rapid learning healthcare system, a new clinical program called the Precision Oncology Program (POP) was created in New England. The POP integrates generalized knowledge about molecular medicine in cancer with a database of observations from previously treated veterans. The program assures access to modern genomic oncology practice in the veterans affairs (VA), removes disparities of access across the VA network of clinical centers, disseminates the products of learning that are generalizable to non-VA settings, and systematically presents opportunities for patients to participate in clinical trials of targeted therapeutics.


2020 ◽  
Vol 25 (11) ◽  
pp. 1897-1904
Author(s):  
Jihyeob Mun ◽  
Gildon Choi ◽  
Byungho Lim

2015 ◽  
Vol 20 (9) ◽  
pp. 1044-1048 ◽  
Author(s):  
Araz A. Raoof ◽  
Jeroen Aerssens

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