Columbia Joins International Consortium to Advance Precision Cancer Medicine

Project GENIE, an ambitious consortium organized by the American Association for Cancer Research (AACR), has recently gained 11 new institutions, including Columbia University’s Herbert Irving Comprehensive Cancer Center (HICCC).

An international cancer registry built through data sharing, Project GENIE, which stands for Genomics Evidence Neoplasia Information Exchange, brings together leading institutions in cancer research and treatment in order to provide the statistical power needed to improve clinical decision-making, particularly in the case of rare cancers and rare genetic variants in common cancers. Additionally, the registry, established in 2016, is powering novel clinical and translational research. In its first two years, Project GENIE has been able to accumulate and make public more than 39,000 cancer genomic records, de-identified to maintain patient privacy. 

Within the next few years for instance, users can turn to this database, gain critical insight about cancer patient profiles that could help them make better, more precise treatment decisions for patients or to advance research efforts; Project GENIE’s database could include, for example, information on malignant tumor development, and data for which drug or drug combination best treated a specific tumor type. The idea of Project GENIE is to be a repository for the largest possible amount of clinical-grade genomic and clinical outcomes data.

“Joining Project GENIE gives us an opportunity to contribute to an international precision clinical oncology effort to understand how to use genomic sequencing information to improve patient response in clinical trials,” says Cory Abate-Shen, PhD, interim director of HICCC and Michael and Stella Chernow Professor of Urological Oncology. In turn, Columbia, which has committed to profiling advanced cancer patients using a combination of genetic panels, exome and mRNA profiles, will be a significant contributor to this endeavor. 

“Due to our ongoing commitment and leadership in precision medicine, Columbia University Irving Medical Center and the Herbert Irving Comprehensive Cancer Center is well positioned to add to this effort,” says Richard D. Carvajal, MD, director of experimental therapeutics and melanoma service at CUIMC. “We will provide our expertise in molecular pathology, systems biology and cancer therapeutics to this international effort to benefit our own patients and patients globally.” 

At Columbia, Project GENIE is being led by Dr. Carvajal and Raul Rabadan, PhD, in collaboration with Dr. Abate-Shen, Andrea Califano, DrGary Schwartz, MD and Dr. Kevin Roth. Collectively, the team brings an exceptional level of cancer research expertise to the project in such diverse areas as systems biology, theoretical physics, mathematics, medicine, oncology and hematology. 

“Columbia has developed unique methodologies in the space of both longitudinal mutational profiling, to understand, for instance, mutational changes in relapsed vs. initial tumors, as well as in the alignment of drugs to individual tumors using mRNA-based analytical methods that have been CLIA certified by the New York State Department of Health,” says Dr. Califano, chair of the Department of Systems Biology, Clyde and Helen Wu Professor of Chemical and Systems Biology and an associate director at HICCC. “The [Genie] repository will allow integration of large-scale genetics with some of the RNA-based studies we are conducting at Columbia, such as the recently initiated N-of-1 studies in pancreatic cancer, pediatric malignancies and in patients with 14 aggressive malignancies who are progressing rapidly on multiple lines of treatment.” 

A significant advantage of Project GENIE is the access to cohort sizes that are not achievable by any individual institution, on its own. This access, notes Dr. Califano “allows us to perform critical retrospective and stratification analyses that will help us plan future studies as well as discover potentially cryptic dependencies in the genome, for instance as it relates to outcome or response to treatment.” 

Columbia’s Department of Pathology and Cell Biology and the Laboratory of Personalized Genomic Medicine (PGM) already generates clinical-grade cancer genomics data for patients treated at Columbia, and has uploaded trial genomics data onto the GENIE data-sharing repository. 

“No one institution treats enough cancer patients of all cancers—especially rare cancers—to generate data with enough statistical power to inform clinical decision making,” notes Dr. Mahesh Mansukhani, director of PGM and associate professor of pathology and cell biology.

By participating in this project, “researchers at Columbia/HICCC will have the opportunity to access a large patient database to extract clinically meaningful information about links between patient-specific cancer-related genetic alterations, treatment responses and outcomes,” adds Dr. Roth, who chairs the Department of Pathology and Cell Biology. 

Project GENIE’s registry is providing the research community with a slew of uses, including validating biomarkers, identifying new drug targets, and adding new genetic mutations to existing drug labels, to name a few; the AACR has said it will work closely with the FDA to ensure that the registry contains data that could be accepted as evidence supporting regulatory approval. 

The hope is that the repository continues to grow as more patients are treated at the participating centers and as new institutions join the project. “As we welcome new members, we look forward to accelerating the pace at which this revolutionary initiative will harness cancer genomics research to enhance the future utility of precision medicine in the treatment of cancer and for the benefit of patients around the world,” says AACR chief Margaret Foti, PhD, MD.

In this latest milestone, Columbia joined the effort with other leading institutions, including Children’s Hospital of Philadelphia, Duke University (Duke Cancer Institute) and Wake Forest University Health Sciences, among others. (The complete list here.) 

Says Dr. Carvajal, “Project GENIE is a bold collaboration that will accelerate and enhance our ability to truly bring precision oncology to our patients … We are proud and excited to be one of 19 leading cancer centers to contribute our clinical-grade genomic and clinical outcomes information to this one-of-a-kind registry.”

-Melanie A. Farmer