Collaborating to Advance Cancer Precision Medicine

Launched in 2015, AACR Project GENIE® is powering advances in most cancers precision medication by way of a global collaboration of prime most cancers facilities which might be sharing knowledge for all to entry.

Charles L. Sawyers, MD, FAACR, has been a pacesetter within the subject of focused most cancers therapies since its earliest phases, together with enjoying a serious role in the development of imatinib (Gleevec), a focused remedy for continual myeloid leukemia permitted by the U.S. Food and Drug Administration (FDA) in 2001. But as he continued to analysis new focused therapies and deal with sufferers with this new class of medicine all through the early 2000s, he got here to a realization: There wanted to be a greater solution to determine subsets of most cancers sufferers with particular genetic mutations that could possibly be focused.

During his tenure as President of the American Association for Cancer Research (AACR) in 2013 and 2014, Dr. Sawyers turned that epiphany into a serious initiative—AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE). The aim was to create a publicly accessible most cancers registry with the real-world genomic and scientific knowledge crucial to assist enhance scientific decision-making and speed up the tempo of advances in most cancers precision medication. But at the moment, next-generation sequencing know-how was solely simply rising, so few establishments might afford to profile tumor genomes—and seize details about genetic alterations—in the course of the affected person’s diagnostic workup.

“I was aware of about eight to 10 cancer centers doing this,” he defined. “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 introduced eight of these establishments collectively to put the preliminary seeds for Project GENIE. On November 6, 2015, the AACR publicly introduced the launch of Project GENIE on the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting in Boston. Less than two years later, in January 2017, the consortium introduced the primary public knowledge launch for the Project GENIE registry, which included practically 19,000 samples. Today, as Project GENIE approaches its 10-year anniversary, the registry has grown to incorporate greater than 250,000 sequenced samples from greater than 200,000 sufferers and has grown to incorporate 20 collaborating establishments.

“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,” mentioned Margaret Foti, PhD, MD (hc), chief government 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 most cancers neighborhood now absolutely sees Dr. Sawyers’ imaginative and prescient, it took slightly convincing to initially align most cancers facilities round 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,” defined Nikolaus Schultz, PhD, from Memorial Sloan Kettering Cancer Center and an ex officio member of Project GENIE’s government 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 because the founding chairperson for GENIE from 2015 to 2020, set this precedent by establishing the primary partnership inside the GENIE consortium. Representing Memorial Sloan Kettering Cancer Center, he labored with Barrett J. Rollins, MD, PhD, to get Dana-Farber Cancer Institute on board. With these two most cancers facilities aligned and the AACR serving because the sincere dealer for the mission, the opposite six unique establishments quickly adopted. Over the years, the consortium hasn’t simply grown in measurement but in addition attain with collaborating establishments 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,” defined 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 persistently labored over these previous 10 years so as to add new analytes and broaden the information sorts within the registry. As a part of this mission, the Biopharma Collaborative (BPC) was launched in 2019 to gather extra scientific knowledge. So far, this coalition of 10 biopharmaceutical firms has added knowledge from greater than 19,000 de-identified sufferers throughout 10 most cancers sorts, however the aim is to finally add scientific knowledge from about 50,000 sufferers.

“Through the BPC, GENIE has added complete clinical longitudinal timelines for thousands of patients,” Dr. Schultz defined. “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 medication and the care of sufferers. 

“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 mentioned. “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 feasible that a few of these sufferers had been handled with that drug off label because it targets the identical mutation, Dr. Sawyers defined. And by way of Project GENIE, clinicians can examine whether or not the drug led to a constructive or damaging end result for these sufferers, which might assist information remedy selections for different sufferers who’re discovered to have that mutation. 

“As oncologists, we know that patients with the same cancer type can respond differently to treatment,” Dr. Bedard mentioned. “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 knowledge from Project GENIE may also be used to function a pure historical past cohort in scientific trials. Since it may be arduous to search out sufficient sufferers with a uncommon mutation to fill a randomized scientific trial, knowledge from sufferers being handled with the investigational drug can as an alternative be in contrast with real-world knowledge from sufferers who had been handled with different therapies. This was the case in 2020 when Amgen used real-world knowledge from Project GENIE—in addition to the Flatiron Health-Foundation Medicine Clinico-Genomic Database—to use for accelerated approval for sotorasib (Lumakras). In May 2021, the FDA granted sotorasib accelerated approval for the remedy of sufferers with KRAS G12C-mutated non-small cell lung most cancers, making it the first-ever permitted 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,” mentioned Shawn M. Sweeney, PhD, the senior director of the AACR Project GENIE Coordinating Center.

Project GENIE has additionally change into a useful resource for researchers exploring a variety of areas, together with exploring new therapeutic targets, testing synthetic intelligence (AI) platforms, understanding the event of early-onset cancers, defining affected person populations for scientific trials, and way more. As of July 2025, knowledge 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,” mentioned 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’ unique imaginative and prescient of an open most cancers registry with deep scientific annotations and genomic knowledge on each affected person within the registry—one thing Dr. Sweeney believes they may obtain inside the subsequent 5 to 10 years—the query turns into what’s subsequent for this groundbreaking initiative?

For one, Project GENIE has established a machine studying and AI working group to check ways in which the know-how could make their knowledge assortment and harmonization strategies much more environment friendly.

“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 defined. “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 knowledge parts must be manually annotated, Dr. Kehl mentioned that might additionally result in extra real-time incorporation of information into the registry, comparable to outcomes from circulating tumor DNA checks or digital pathology imaging. Dr. Sweeney added that the usage of AI fashions might additionally lead to a deeper scientific evaluation of affected person knowledge. For instance, AI might probably uncover insights from these digital pathology photographs that people could miss.

Another aim that Dr. Sweeney hopes to perform inside the subsequent 5 years is to make a good bigger influence for uncommon cancers. One method he believes they may obtain that’s by present FDA-approved medication to research if Project GENIE has any knowledge to assist a brand new indication for a most cancers with a uncommon mutation. 

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

Other future plans for Project GENIE embody the potential addition of instruments that will make it simpler for individuals with out computational experience to grasp and analyze the information, the power to seek for scientific trial matches for sufferers with uncommon 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 mentioned. “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.”