Key Takeaways
- Creating new models of drug-resistant cancer: ATCC and the Broad Institute collaborated to develop CRISPR-engineered drug-resistant isogenic cell lines that replicate clinically observed resistance mechanisms to targeted therapies. The initial effort resulted in 13 isogenic non-small cell lung cancer (NSCLC) cell lines, each engineered to harbor a defined resistance mechanism to the EGFR inhibitor osimertinib.
- Expanding the Cancer Dependency Map: The models will be integrated into the Cancer Dependency Map (DepMap) to help build a response and resistance map (ResMap) of therapeutic vulnerabilities in cancer.
- Advancing precision oncology: The models allow researchers to directly compare drug-sensitive and resistant cancer cells to uncover new therapeutic targets and drug combination strategies.
- Providing an open resource for global researchers: The engineered models and associated genomic datasets will be made available through ATCC and the DepMap portal to support cancer research, functional genomics, and AI-driven drug discovery.
MANASSAS, Va., and CAMBRIDGE, Mass., April 20, 2026 (GLOBE NEWSWIRE) -- ATCC and the Broad Institute of MIT and Harvard today announced new research describing the development of engineered isogenic cancer models designed to replicate resistance to targeted therapies, beginning with osimertinib, the latest-generation epidermal growth factor receptor (EGFR) inhibitor used to treat non-small cell lung cancer (NSCLC) with EGFR mutations.
The work addresses a critical challenge in oncology—treatment resistance that emerges over time. EGFR-mutant lung cancer was among the first subsets of a major epithelial cancer where directly targeting an oncogene was associated with marked clinical benefit. While targeted therapies have significantly improved overall survival, resistance inevitably develops.
Understanding resistance mechanisms is essential for identifying combination therapies capable of producing durable responses and potentially disease-free remissions. Developing resistant models directly from patient tumors, however, can take years due to the scarcity of samples. In contrast, engineering resistance mechanisms in controlled laboratory models allows researchers to systematically study multiple escape pathways much faster.
To accelerate discovery, scientists from ATCC and the Broad Institute collaborated to engineer a panel of drug-resistant NSCLC models using CRISPR gene editing and gene overexpression techniques. These models systematically model the resistance mechanisms that arise in patients treated with osimertinib.
“With this powerful new set of tools, drug-sensitive and drug-resistant cancer cells can be studied side by side to understand therapeutic resistance and the underlying drivers,” said Ruth Cheng, PhD, CEO of ATCC. “By creating and providing these cancer models along with a rich data-set to the global research community, our hope is to reveal hidden targets and combination strategies that turn today’s treatment failures into tomorrow’s breakthrough. We look forward to extending this approach to additional cancer types.”
Engineering drug-resistant lung cancer models
Led by William R. Sellers, MD, Director of the Cancer Program at the Broad Institute, Fang Tian, PhD, Director of Biological Content at ATCC, and Francisca Vazquez, PhD, Director of DepMap at the Broad Institute, the ATCC-Broad team identified representative classes of resistance mechanisms to osimertinib. They then selected three disease-representative, osimertinib sensitive NSCLC cell lines as the foundation for developing the new isogenic drug- resistant cell models.
ATCC engineered the selected authenticated cell lines with resistance mechanisms using CRISPR-based methods. The six resistance mechanisms included:
- PIK3CA E545K mutation
- KRAS G12D mutation
- BRAF V600E mutation
- EGFR C797S mutation
- CCDC6-RET fusion
- TPM3 - NTRK1 fusion
In addition, scientists at the Broad Institute are generating additional resistant cell lines driven by gene amplification mechanisms using overexpression methods.
These engineered isogenic model systems allow researchers to compare genetically matched cancer cells that differ only by a specific resistance alteration—providing a powerful framework to study how tumors evolve under targeted therapy.
Building a response and resistance map for cancer
The models will be integrated into the Cancer Dependency Map (DepMap), a global effort to identify genetic vulnerabilities across hundreds of cancer cell models.
The collaboration also contributes to the development of a Response and Resistance Map (ResMap)—an emerging framework designed to systematically characterize how cancers respond to therapy and how resistance evolves.
“Drug resistance remains one of the most significant barriers to durable cancer treatment,” said Kirsty Wienand, PhD, Sr Research Scientist in DepMap at the Broad Institute. “Systematically engineering resistance mechanisms in well-characterized cell models allows us to study how tumors adapt to targeted therapy. Integrating these models into DepMap will help researchers worldwide identify new vulnerabilities and potential therapeutic combinations.”
Enabling and accelerating discovery across the global research community
The collaboration ensures that both the biological models and the associated data will be widely accessible to the scientific community.
- Data will be integrated into the DepMap portal, with links to the corresponding ATCC cell line identifiers.
- The engineered cell lines will be distributed globally through ATCC following authentication and quality control.
Systematically engineering clinically relevant resistance mechanisms in lung cancer models, the collaboration establishes a scalable framework for studying how tumors escape targeted therapies. The resulting models and datasets will help researchers identify new vulnerabilities and therapeutic strategies to overcome drug resistance and improve outcomes for patients with cancer.
By combining advanced cell engineering, functional genomics, and computational biology, the collaboration provides a powerful resource for studying drug resistance, cancer vulnerabilities, and precision oncology strategies.
Research to be presented at industry event
ATCC and Broad Institute will present the research findings at the American Association for Cancer Research® (AACR) Annual Meeting 2026, April 17–22 in San Diego.
Title: Engineering isogenic models harboring resistance mechanisms to the latest-generation EGFR inhibitor in non-small cell lung cancer
Session Category: Experimental and Molecular Therapeutics
Session Title: Drug Resistance 2: Tyrosine Kinase Inhibitors
Date: April 22, 2026
Time: 9:00 AM – 12:00 PM
Location: Poster Section 11
Poster Board: 8
Poster Number: 7029
About ATCC
ATCC is a premier global biological materials and information resource and standards organization and the leading developer and supplier of authenticated cell lines, microorganisms, and associated data for academia, industry, and government. With a history of scientific contributions spanning more than a century, ATCC offers an unmatched combination of being the world’s largest and most diverse collection of biological reference materials and data, and is a mission-driven, trusted partner that supports and encourages scientific collaboration. ATCC products, services, partnerships, and people provide the global scientific community with credible, advanced model systems to support complex research and innovations in basic science, drug discovery, translational medicine, and public health. ATCC is a 501(c)(3) nonprofit organization headquartered in Manassas, Virginia, with research and technology centers of excellence in Gaithersburg and Germantown, Maryland.
Media Contact:
Samantha Paro
Senior Manager, Corporate Communications & Public Affairs
ATCC
pr@atcc.org
About the Broad Institute
Broad Institute is an independent, non-profit research organization whose mission is to understand the roots of disease and close the gap between new biological insights and impact for patients.
Founded in 2004 by the visionary Los Angeles philanthropists Eli and Edythe Broad, the Broad Institute exists at the intersection of scientific disciplines, convening scientists and other experts from genomics, cell biology, chemistry, engineering, neuroscience, therapeutics, artificial intelligence/machine learning, computational biology, and public health. The Broad Institute engages thousands of scientists from MIT, Harvard, Harvard’s primary teaching hospitals, other academic institutions, and leading corporate partners in the pharmaceutical and biotechnology industries, all of whom share the goal of translating research findings into safe and effective therapeutic interventions for all common and rare diseases.
Media Contact:
Karen Zusi-Tran
kzusi@broadinstitute.org
*Not affiliated with or endorsed by AACR.
