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Ex Vivo Three-dimensional Tumor Growth Assay: 3DX-TGA
With an ~7% likelihood of regulatory approval, oncology drug registration failure rates lead all therapeutic areas. Further complicating the drug development process, preclinical oncology models poorly reflect tumor tissue biology and produce a high level of false positive and negative data. Yet, monocellular two-dimensional (2D) tissue culture remains the preferred platform for most laboratory preclinical studies. The popularity of 2D tissue culture was driven predominantly by fast and dependable proliferation of human tumor cells rather than alignment to the pathophysiology of human cancer.
Nevertheless, rational drug combinations and identification of clinically meaningful drug targets persist as major challenges in oncology, and each can be meaningfully addressed by using more diverse and biologically relevant preclinical models. Ex vivo tumor tissue transplant models, such as patient-derived xenografts (PDX) offer greater model diversity and more faithfully reflect patient tumor genetics. However, cost and scalability barriers tend to limit widespread and practical model utility. In addition, there remains a strong selection bias for autocrine human tumors that can quickly adapt to a cross-species mouse host. Our data suggest that model ‘humanization’ improves ex vivo modeling take rates.
Praveen Nair#, Dileep Nair#, Kaede Hinata#, Cyrus Mirsaidi, Junjie Wu, Yong Hu, Brett Hall#
# Molecular Response LLC
Poster on the establishment, serial propagation and molecular characterization of 300+ ex vivo 3D (3DX) models spanning 16 tumor indications, as a practical alternative to PDX models. Presented by Brett Hall, Ph. D., at AACR 2017.
hTME-3DX Screen and Verify™ is based on the proprietary primary tumor bank and 3D drug screening platform that was developed by Molecular Response, through a large body of academic and commercial research over the past decade, as well as, internal expertise in ex vivo cell cultures and human tumor sample preservation.