The Developmental Therapeutics Core (DTC), under the umbrella of the Center for Developmental Therapeutics (CDT), provides services focused on supporting the translation of new therapeutics to the clinic. The DTC supports grant applications and can act as an already established translational Core on multi-investigator U and P type grants. In addition to supporting basic research leading to drug translation, the DTC also provides support to clinical investigators interested in advancing new compounds into clinical trials including drug assessment and clinical protocol support.
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Miodragovic, D.U., Quentzel, J.A., Kurutz, J.W., Stern, C.L., Ahn, R.W., Kandela, I., Mazar, A., and O'Halloran, T.V. (2013). Robust structure and reactivity of aqueous arsenous acid-platinum(II) anticancer complexes. Angewandte Chemie 52, 10749-10752.
Dalva-Aydemir, S., Bajpai, R., Martinez, M., Adekola, K.U., Kandela, I.K., Wei, C., Singhal, S., Koblinski, J.E., Raje, N.S., Rosen, S.T., et al. (2014). Targeting the Metabolic Plasticity of Multiple Myeloma with FDA Approved Ritonavir and Metformin. Clinical cancer research : an official journal of the American Association for Cancer Research.
Patient-Derived Xenograft (PDX) models represent the cutting edge of cancer drug development, increasing our ability to advance novel, active agents into patients. A joint effort between the Pathology Core Facility and the Center for Developmental Therapeutics, the project uses a systematic approach to develop models across multiple tumor histologies in a way that benefits the entire institution. This repository allows many basic oncology research questions to be addressed using annotated tissue and models that closely resemble human cancer rather than cell lines.
Xenograft model or heterotransplantation of human cancer cell lines into immunodeficient mice has served for decades as the major preclinical screen for the development of novel cancer therapeutics. However, current cell line-xenograft tumor preclinical models could not predict success of oncology drug development. When the model of the xenograft tumor established from cancer cell line is used, novel therapeutics that were 97% successful in in vivo studies fail in clinic.
We have developed PDX tumor models of 10 different types of human cancer including:
Patient derived xenograft (PDX) tumor models emerged as a new approach for preclinical testing of novel anticancer compounds in vivo due to its preservation of key features, which includes invasiveness, stromal reaction, tumor vasculature and cellular diversity of human carcinomas. In contrast to a cell line-xenograft tumor model, PDX tumors are established from the transplantation of fresh tumor tissue from a cancer patient into a immunodeficient mouse.
Fresh tumor samples were obtained from over 40 cancer patients immediately after surgical resection. Initially, we transplanted a small piece of fresh human tumor tissue either subQ or intraperitoneally and then passaged the xenograft tumors in mice to expand the amount of tumor tissue frozen. We reproducibly use our frozen stock to establish PDX tumors for future in vivo studies. All PDX tumor models are available to NU research community. Please contact Irawati (Angki) Kandela, Assistant Director of the Developmental Therapeutics Core, for more information about program development and PDX tumor availability.
The project is supported by the Baskes Foundation and Robert H. Lurie Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Baskes Foundation and Robert H. Lurie Comprehensive Cancer Center.
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