Comparative Oncology Program Laboratory

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Laboratory activities and projects carried out by the Comparative Oncology Program (COP) laboratory have the specific goal of improving the understanding of the impact of anti-cancer agents on comparative aspects of metastasis biology by virtue of parallel study of murine, canine and human cell lines in a variety of in vitro and in vivo model systems. Data generated in this manner improves understanding of spontaneous canine osteosarcoma (OS) models and could be employed to answer unique in vivo questions regarding the anti-metastatic potential of agents, via the Comparative Oncology Trials Consortium (COTC) clinical trial mechanism. To extend our investigations into the comparative aspects of OS in dogs to humans, we have recently initiated the DOG2 project: Decoding the Osteosarcoma Genome of the Dog. The DOG2 project fulfills the main mission of the NCI-COP, which is to strategically position the canine cancer patient in studies of cancer biology and drug development, in order to improve outcome for both dogs and humans. The COP has a longstanding focus in osteosarcoma (OS) biology and clinical trials. OS is an aggressive pediatric/AYA malignancy and the most common malignant bone tumor in children and adolescents. OS is also a common canine cancer with strikingly similar clinical presentation and natural history; studies from our group and others strongly suggest a shared molecular landscape. While dogs largely develop OS in adulthood, the similar genomic features and clinical disease characteristics underscore the notion that age does not distinguish canine OS from the disease in children. We recognize that osteosarcoma is a complex disease and success is unlikely with a single approach. Therefore, to expand this work it is necessary to identify additional targets and drugs. Collectively this work is designed to address the following strategic priorities: 1. Improved knowledge of comparative OS cancer biology to enhance dog to human translation; 2. Discovery of new targets and companion biomarkers in support of drug development; 3. Assessment and prioritization of new therapeutic strategies in preclinical models; 4. Harmonization of comparative canine and human oncology clinical trials to advance new therapeutic concepts. Using our existing high-quality clinically-annotated biospecimen repository of ~ 400 canine OS patient sample sets, unique to the NCI, we have established cohorts of sequencing data across multiple platforms and have published the first analyses relating to these data. First, we have established through 2 approaches that transcriptional profiles identified from treatment-naive primary tumor tissue in dogs have prognostic value in both dogs and humans with osteosarcoma. Second, we have applied a combined CNV and FISH assay development plan to identify and validate prognostic copy-number profiles in dogs with a clinically-deployable companion biomarker. We have recently published the first studies of spatial profiling of canine tumor tissue using the nanoString GeoMX platform to identify and characterize tissue for functionality of defined tissue compartments (e.g. tumor-associated lymphoid aggregates or TLS). Work performed since the last yearly report has discovered that tumor methylation status and MYC copy number have prognostic significance in dogs as has been recently reported in humans. We are also working in metastatic disease to identify gene expression patterns between tumor and tumor-adjacent and tumor-distant 'normal' tissues to characterize gene expression changes that may represent druggable targets. Samples are readily available from lung, liver, kidney and other distant sites that provide the ideal proving ground for therapeutic targets for comparative study.