NCI-supported Cancer Model Development Centers (CMDCs) and HCMI consortium members will create about 1,000 new cancer models. At present, the models are being derived from diverse tumor subtypes from different populations. The models and case-associated clinical and molecular data are available to cancer researchers as a community resource.
The sequence information from tumor-derived models, normal tissue, and parent tumor, as well as patients’ de-identified clinical data, are available to researchers through the NCI’s Genomic Data Commons (GDC).The European Genome-phenome Archive at the European Bioinformatics Institute is the repository for the sequencing data generated by the European consortium members. Availability of these datasets allows for correlation of genomic data with clinical characteristics. The models are available to researchers through a third-party distributor.
Many of the cancer cell 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 derived next-generation cancer model. The information collected are made available to the end-user.
Next-generation Cancer Models
Next-generation cell culture models, such as organoids, conditionally reprogrammed cells (CRC), or optimal growth condition models introduce the opportunity to propagate primary normal and cancer cells. The term organoid here refers to a three-dimensional (3D) structure grown from tumor cells in vitro that comprises organ-specific cell types. The CRC methodology uses unique cell growth media supplemented with growth factors to enable cancer model development and growth for in vitro experiments. The organoid, CRC, and optimum growth condition methods have been used, with some modifications, to grow tumor tissues in research.
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 provides 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, glioblastoma, gastroesophageal, lung, melanoma and pancreas. Models from rare adult and pediatric cancers including neuroblastoma, osteosarcoma, Wilms tumor, rhabdomyosarcoma and Ewing sarcoma have been developed by HCMI. Model generation from new cancer types including kidney, ovarian, and endometrial cancers is currently ongoing. The model list along with their associated case report forms (CRFs) will be updated as more cancers are represented by HCMI models in the future.
Developing Models to Address Cancer Disparities
NCI has made a strong commitment to decrease cancer 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 support research supplement awards for collection of tumors and clinical data from racial and ethnic minority populations for next-generation cancer model development.
Center for Cancer Genomics director Dr. Staudt mentioned the HCMI’s collaboration with the CRCHD in his blog post “Continuing Our Work in the Time of Two Pandemics”.
Model Characterization and Standardization
HCMI models and associated tumor and normal tissues are characterized using standard operating procedures for clinical and molecular data.
HCMI uses cancer type-specific Clinical Data Working Groups to generate Case Report Forms (CRFs). Clinical Data Working Groups are composed of disease experts and pathologists who contribute to the content of the cancer type-specific CRFs used to collect HCMI clinical data. These CRFs function to standardize the clinical data that is collected from participating HCMI sites.
To help standardize molecular characterization, sequence data of NCI-supported models and associated normal and tumor tissue are harmonized through NCI's Genomic Data Commons (GDC). Available datasets are at the GDC data portal. This includes datasets from
150x whole exome (WXS),
15x whole genome (WGS), and
120 million read RNA-sequencing.