Co-Clinical Imaging Resource Program (CIRP): Bridging the Translational Divide to Advance Precision Medicine

Abstract

The National Institutes of Health's (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its overarching mission is to advance the practice of precision medicine by establishing consensus-based best practices for co-clinical imaging research by developing optimized state-of-the-art translational quantitative imaging methodologies to enable disease detection, risk stratification, and assessment/prediction of response to therapy. In this communication, we discuss our involvement in the CIRP, detailing key considerations including animal model selection, co-clinical study design, need for standardization of co-clinical instruments, and harmonization of preclinical and clinical quantitative imaging pipelines. An underlying emphasis in the program is to develop best practices toward reproducible, repeatable, and precise quantitative imaging biomarkers for use in translational cancer imaging and therapy. We will conclude with our thoughts on informatics needs to enable collaborative and open science research to advance precision medicine.

Keywords: CT; MR; cell transplant model (CTM); co-clinical trial; genetically engineered mouse model (GEMM); informatics; patient-derived tumor xenograft (PDX); precision medicine; preclinical PET; quantitative imaging.

Figure 1.

Organizational structure of Co-Clinical Imaging Resource Program (CIRP). Members of the steering committee (SC) comprise investigators from within U24 awardees. The SC oversees the activities of 3 working groups (WGs) (animal models and co-clinical trials, image-acquisition and data processing [IADP], and informatics and outreach [IMOR]) focused on practical aspects of co-clinical imaging. Individuals not directly funded by the U24 mechanism may petition to join the CIRP network as associate members. Associate members are then affiliated with one or more of the WGs.

Figure 2.

The co-clinical precision medicine design paradigm. In the co-clinical study design, mouse models (patient-derived tumor xenograft [PDX], genetically engineered mouse model [GEMMs], or cell transplant models [CTMs]) are developed to match the patient’s tumor genotype or subtype. In parallel with the clinical trials, these patient-matched co-clinical models are used to assess the sensitivity of tumors to drugs or drug combinations, and thus inform the clinical trial. (Adapted from Clohessy and Pandolfi (9).)

Figure 3.

Generation of CTMs for use in co-clinical trials. Investigators isolate bone marrow from a donor animal and transduce enriched hematopoietic stem cells (HSCs) or the total population of bone marrow cells with recombinant retroviruses or lentiviruses expressing critical oncogenes for a target disease. These types of viral vectors integrate into the genome of cells, ensuring stable expression of key oncogenic mutations in HSCs and transmission of mutations to more differentiated hematopoietic cells.