Preclinical Evaluation of Therapeutic Compounds in Mouse Models for Cancer at the Center for Advanced Preclinical Research (CAPR)

Authors

• L Szabova
• R El Meskini
• T Vilmas
• B Karim
• S Jones
• S Sharan
• S Kozlov
• Z Weaver Ohler

Abstract

The Center for Advanced Preclinical Research (CAPR), established in 2008 and currently directed by Dr. Shyam Sharan, is a CCR-supported resource to carry out in vivo preclinical research using well characterized mouse cancer models. Its mission is to develop, disseminate, and apply reproducible preclinical practices effective in guiding clinical research toward improved cancer patient outcomes. We partner with FNLCR and CCR core facilities to achieve a broad range of capabilities (e.g. efficacy studies; https://ccr.cancer.gov/capr-home) required for effective preclinical cancer research. The goal is to evaluate preclinical compounds or existing drugs or biologics (therapeutics) for the identification of new indications or new combinations or sequences of dosing using genetically engineered mouse (GEM) models and GEM-derived allograft (GDA) models as the experimental platform. Genetically engineered mouse models of cancer recapitulate the tumor microenvironment, including the intact immune response, more accurately and produce more representative tumors than classic human cell line xenograft models. For comparison, we are also establishing patient-derived xenografts in collaboration with NCI Investigators. Since its inception, CAPR has been actively collaborating with academic and NCI investigators, as well as foundations and pharmaceutical companies, to perform preclinical studies in glioblastoma, melanoma, lung, ovarian, and pancreatic cancers. As an example, we will present preclinical evaluation data from ovarian and pancreatic carcinoma models. With the increasing interest of CCR investigators to partner with CAPR, the CAPR Oversight Committee (OC) has been established by CCR leadership at the end of 2015, and CAPR Request for Application (RFA) was announced to CCR research community in summer of 2016. The purpose is to support rigorous, preclinical studies in mouse models with the goal of establishing the rationale for translation of preclinical findings to pre-Phase I or Phase I clinical studies.

Scientific Focus Area: Cancer Biology

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