NCI-funded Cancer Model Development Centers (CMDCs) and HCMI consortium members are creating about 1,000 new cancer models. At present, the models are being derived from diverse tumor subtypes from different populations. As HCMI-developed models are made available, related clinical and molecular data will be available to cancer researchers as a community resource to further study the relationship between laboratory findings and clinical biology.
The tumor-derived models, normal tissue, and parent tumor generated from the NCI-supported CMDCs will be sequenced, and this information, as well as patients’ clinical data, will be available to researchers through the NCI’s Genomic Data Commons (GDC).The European Bioinformatics Institute will house the sequencing data as well as patients’ clinical data for models generated by European consortium members. Availability of these datasets will allow for correlation of genomic data with clinical characteristics. The models will be available to researchers through a third-party distributor.
Many of the cancer lines that are commonly used in cancer research were established decades ago. These cell lines have been useful for in vitro experiments to study cancer biology, biochemistry, and drug targets. However, drawing conclusions about how in vitro observations may relate to clinical biology is challenging because cancer cell lines:
- lack the cellular complexity and architecture of human tumors, which introduces possibility that genetic drift may have occurred after the cell line was established.
- are not associated with clinical information from the patient.
- genomic relatedness to the parent tumor is unknown, and molecular characterization including assessment of genomes and transcriptomes of these cell lines, until recently, were mostly unavailable.
- from diverse racial and ethnic groups and rare cancers are seldom represented in currently available cell lines.
HCMI addresses the deficiencies in current models by collecting patients’ clinical data and assessing, as much as possible, the genomes and transcriptomes of the parent tumor, case-matched normal tissue, and the resulting next-generation cancer model. The information collected will be made available to the end-user.
Next-generation Cancer Models
Next-generation cell culture methods, such as organoids and conditionally reprogrammed cell (CRC) models, introduce the opportunity to propagate primary normal and cancer cells. The term organoid has been used previously; here it refers to a three-dimensional (3D) structure grown from stem cells in vitro that comprises organ-specific cell types. The CRC methodology was originally developed for epithelial cell types. The organoid and CRC methods have been used to successfully grow human normal tissues from multiple different organs and have been applied, with some modifications, to grow tumor tissues.
Next-generation cancer model systems present a unique opportunity for the scientific community to study individual human tumors in vitro to further advance knowledge in a variety of research areas such as cancer biology, biochemistry, and exposure to perturbagens. The next-generation cancer models that result from the efforts of HCMI will serve as excellent tools to support precision oncology research and give insight into the pathways that influence tumor progression.
The goal of HCMI is to generate models from many human cancer subtypes, including breast, colorectal, esophageal, glioblastoma, bladder, thyroid, and pancreas. Model development for rare, pediatric cancers including neuroblastoma, Wilms tumor, and Ewing sarcoma has begun. In the future, models may be generated from ovarian, head and neck, kidney and rare cancer types.
NCI has made a strong commitment to decrease health disparities by supporting model development from racially and ethnically diverse populations. OCG has partnered with the Center to Reduce Cancer Health Disparities (CRCHD) to fund several research supplement awards for collection of tumors and clinical data from racial and ethnic minority populations.
Model Characterization and Standardization
HCMI models will be characterized and standardized at the level of clinical and molecular data. Clinical Data Working Groups, composed of clinicians, contribute to the content of the cancer type-specific Case Report Forms (CRFs) used to collect HCMI clinical data. These CRFs function to standardize the clinical data that is collected from participating HCMI sites. For NCI-supported models, the associated molecular data will be harmonized through NCI’s Genomic Data Commons so that the data can be compared across multiple patients.