Collaborating to Advance Cancer Precision Medicine Globally—10 Years of AACR Project GENIE®

Launched in 2015, AACR Project GENIE® is powering advances in cancer precision medicine through an international collaboration of top cancer centers that are sharing data for all to access.

Charles L. Sawyers, MD, FAACR, has been a leader in the field of targeted cancer therapies since its earliest stages, including playing a major role in the development of imatinib (Gleevec), a targeted treatment for chronic myeloid leukemia approved by the U.S. Food and Drug Administration (FDA) in 2001. But as he continued to research new targeted therapies and treat patients with this new class of drugs throughout the early 2000s, he came to a realization: There needed to be a better way to identify subsets of cancer patients with specific genetic mutations that could be targeted.

During his tenure as President of the American Association for Cancer Research (AACR) in 2013 and 2014, Dr. Sawyers turned that epiphany into a major initiative—AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE). The goal was to create a publicly accessible cancer registry with the real-world genomic and clinical data necessary to help improve clinical decision-making and accelerate the pace of advances in cancer precision medicine. But at that time, next-generation sequencing technology was only just emerging, so few institutions could afford to profile tumor genomes—and capture information about genetic alterations—during the patient’s diagnostic workup.

“I was aware of about eight to 10 cancer centers doing this,” he explained. “I could see that each one was going to discover one small thing, perhaps every year or so. But if we pooled our efforts and shared our data, we’d find bigger patterns.” 

So, Dr. Sawyers brought eight of those institutions together to lay the initial seeds for Project GENIE. On November 6, 2015, the AACR publicly announced the launch of Project GENIE at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting in Boston. Less than two years later, in January 2017, the consortium announced the first public data release for the Project GENIE registry, which included nearly 19,000 samples. Today, as Project GENIE approaches its 10-year anniversary, the registry has grown to include more than 250,000 sequenced samples from more than 200,000 patients and has grown to include 20 participating institutions.

“In the 10 years since its inception, AACR Project GENIE has become the largest, fully public registry of cancer genomic datasets and is propelling advances in cancer drug discovery and improved patient care,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “To conceptualize and launch such a novel and impactful project was sheer brilliance on Dr. Sawyers’ part, and the entire cancer community will be forever grateful.”

Building the Project GENIE Consortium and Registry 

While the cancer community now fully sees Dr. Sawyers’ vision, it took a little convincing to initially align cancer centers around this data-sharing initiative. 

“When I started in this field 15 years ago, nobody wanted to share any data. Even when you published papers, institutions wanted to withhold the data,” explained Nikolaus Schultz, PhD, from Memorial Sloan Kettering Cancer Center and an ex officio member of Project GENIE’s executive committee. “But GENIE has set a new standard. It’s not only okay to share data, it’s actually our responsibility as cancer centers to share that data.”

Dr. Sawyers, who served as the founding chairperson for GENIE from 2015 to 2020, set this precedent by establishing the first partnership within the GENIE consortium. Representing Memorial Sloan Kettering Cancer Center, he worked with Barrett J. Rollins, MD, PhD, to get Dana-Farber Cancer Institute on board. With these two cancer centers aligned and the AACR serving as the honest broker for the project, the other six original institutions soon followed. Over the years, the consortium hasn’t just grown in size but also reach with participating institutions from France, Spain, the Netherlands, and South Korea.

“Cancer is a global challenge, and to ensure patients worldwide benefit from research, we need data that supports discoveries across diverse regions,” explained Philippe Bedard, MD, from the Princess Margaret Cancer Centre in Toronto and Project GENIE chairperson from 2021 to 2024. “That’s why Project GENIE aims to include data from varied patient populations, reflecting ethnic and racial diversity, different cancer types, and treatment approaches around the world.”

Project GENIE has consistently worked over these past 10 years to add new analytes and expand the data types in the registry. As part of this mission, the Biopharma Collaborative (BPC) was launched in 2019 to collect more clinical data. So far, this coalition of 10 biopharmaceutical companies has added data from more than 19,000 de-identified patients across 10 cancer types, but the goal is to eventually add clinical data from about 50,000 patients.

“Through the BPC, GENIE has added complete clinical longitudinal timelines for thousands of patients,” Dr. Schultz explained. “We now know how these patients were treated and how they responded, which allows us to correlate genomic alterations with their response to treatment.”

Advancing Precision Medicine and Research 

The insights that clinicians and researchers can glean from the Project GENIE registry has led to advances in precision medicine and the care of patients. 

“Because GENIE is now well over 200,000 patients, it is possible to find examples of patients who have a mutation that’s so rare that it was missed by the original cancer sequencing efforts, such as The Cancer Genome Atlas (TCGA),” Dr. Sawyers said. “In several cases, the mutation is in a protein for which there is a drug that was approved for some other indication, but not the cancer these patients have.” 

It is possible that some of these patients were treated with that drug off label since it targets the same mutation, Dr. Sawyers explained. And through Project GENIE, clinicians can check whether the drug led to a positive or negative outcome for these patients, which could help guide treatment decisions for other patients who are found to have that mutation. 

“As oncologists, we know that patients with the same cancer type can respond differently to treatment,” Dr. Bedard said. “Access to a global database with case histories of 150 to 200 patients sharing the same rare genetic alteration as the one in front of you can provide valuable insights into which treatments are most likely to work. That’s an incredibly powerful tool for guiding clinical decisions.”

Dr. Sawyers added that data from Project GENIE can also be used to serve as a natural history cohort in clinical trials. Since it can be hard to find enough patients with a rare mutation to fill a randomized clinical trial, data from patients being treated with the investigational drug can instead be compared with real-world data from patients who were treated with other therapies. This was the case in 2020 when Amgen used real-world data from Project GENIE—as well as the Flatiron Health-Foundation Medicine Clinico-Genomic Database—to apply for accelerated approval for sotorasib (Lumakras). In May 2021, the FDA granted sotorasib accelerated approval for the treatment of patients with KRAS G12C-mutated non-small cell lung cancer, making it the first-ever approved KRAS inhibitor. 

“It was a patient population with high unmet need, so it was a very proud moment for us to be able to support the justifications for the accelerated approval,” said Shawn M. Sweeney, PhD, the senior director of the AACR Project GENIE Coordinating Center.

Project GENIE has also become a resource for researchers exploring a wide range of areas, including exploring new therapeutic targets, testing artificial intelligence (AI) platforms, understanding the development of early-onset cancers, defining patient populations for clinical trials, and much more. As of July 2025, data from Project GENIE has been cited in over 1,550 papers. 

“While GENIE enables a number of different types of analyses that wouldn’t otherwise be possible regarding rare variants and rare cancer types, the data are also increasingly being used as pieces and parcels of much more basic research to drive the directions in which that research should go,” said Kenneth L. Kehl, MD, MPH, from Dana-Farber Cancer Institute and the Project GENIE chairperson from 2025 to 2026. “It’s almost becoming a public utility in a way.”

The Future of AACR Project GENIE

As AACR Project GENIE continues to make strides in fulfilling Dr. Sawyers’ original vision of an open cancer registry with deep clinical annotations and genomic data on every patient in the registry—something Dr. Sweeney believes they will achieve within the next five to 10 years—the question becomes what’s next for this groundbreaking initiative?

For one, Project GENIE has established a machine learning and AI working group to test ways that the technology can make their data collection and harmonization methods even more efficient.

“So much of what we need to understand about clinical outcomes, treatments, and patient characteristics is stored in a scattered unstructured form within the electronic health records,” Dr. Kehl explained. “While we have experience gathering that manually on the scale of thousands of patients, if we’re going to get to tens of thousands and hundreds of thousands, it’s going to require AI-type methods.”

If fewer data elements have to be manually annotated, Dr. Kehl said that could also lead to more real-time incorporation of data into the registry, such as results from circulating tumor DNA tests or digital pathology imaging. Dr. Sweeney added that the use of AI models could also result in a deeper clinical analysis of patient data. For example, AI could potentially uncover insights from those digital pathology images that humans may miss.

Another goal that Dr. Sweeney hopes to accomplish within the next five years is to make an even larger impact for rare cancers. One way he believes they could achieve that is by looking at existing FDA-approved drugs to analyze if Project GENIE has any data to support a new indication for a cancer with a rare mutation. 

“You could make an instant benefit for underserved populations—this is where these kinds of data really come to bear,” Dr. Sweeney said. “That would be a huge win for everybody.”

Other future plans for Project GENIE include the potential addition of tools that would make it easier for people without computational expertise to understand and analyze the data, the ability to search for clinical trial matches for patients with rare mutations, and the continued diversification of the datasets. 

“As AACR Project GENIE continues to grow, it will provide cancer researchers worldwide with actionable data to propel the next wave of discoveries, advancing cancer precision medicine, and transforming cancer patient care,” Dr. Foti said. “The staunch commitment of AACR Project GENIE to provide open, fully accessible data has created a remarkable public utility for the global cancer research community.”