New CRISPR-engineered cancer models decode how tumors outsmart targeted therapies

Overview

Every year, hundreds of thousands of lung cancer patients start treatment with osimertinib, the leading targeted therapy for tumors driven by mutations in the EGFR gene. Most will respond, but nearly all will eventually stop responding as their cancers evolve resistance through a dozen different molecular escape routes. Until now, researchers had to work with messy lab models that made it hard to pin down which genetic change caused which failure.

On April 20, 2026, the American Type Culture Collection (ATCC) and the Broad Institute of MIT and Harvard released 13 precisely engineered cancer cell lines, each genetically identical except for a single resistance mechanism. This gives researchers clean, standardized tools to study exactly how and why treatments stop working. The release matters beyond any single drug.

The models feed into a new initiative called the Response and Resistance Map, or ResMap, which aims to systematically catalog how cancers adapt to therapy across tumor types and drug classes. Combined with the Broad's existing Cancer Dependency Map (DepMap), the panel is made freely available to researchers worldwide. It provides both human scientists and artificial intelligence-driven drug discovery programs with high-quality, unambiguous data needed to design combination therapies that cut off tumor escape routes.

Why it matters

Cancer drug resistance kills more patients than cancer drug failure, and researchers now have the first standardized toolkit to decode it systematically.

Questions about this story

No questions yet — be the first to ask.

Play on this story Voices Debate Predict

Key Indicators

Isogenic cell line models released

Each engineered with a single, defined resistance mechanism to osimertinib, enabling direct comparison against the sensitive parent line.

$7.25B

Osimertinib annual sales (2025)

AstraZeneca's Tagrisso is one of the world's best-selling cancer drugs, underscoring how many patients depend on a therapy that eventually fails.

18–24 mo

Typical time to resistance

Most patients on first-line osimertinib develop resistance within two years, with no single dominant escape mechanism.

1,000+

Cell lines in DepMap

The Broad's Cancer Dependency Map has profiled over a thousand cancer cell lines; the new resistance models expand this resource into a new dimension.

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

Play

Exploring all sides of a story is often best achieved with Play.

Predict 4 ways this could play out. Contrarian picks score more — points lock when the scenario resolves. Log in to play

Timeline Five events from this story — drag them oldest to newest. Log in to play

Connections Sixteen names from the news. Find the four hidden groups of four. Log in to play

People Involved

Kirsty Wienand

Lead researcher on the isogenic resistance model project

Francisca Vazquez

Accepted 2026 AACR Team Science Award on behalf of DepMap team; overseeing integration of resistance models into DepMap and ResMap

Mindy Goldsborough

Leading ATCC's cancer model engineering and distribution efforts

Organizations Involved

ATCC (American Type Culture Collection)

Biological Standards Organization

Co-developed and will distribute the isogenic resistance models

The world's premier repository for authenticated, quality-controlled biological materials, including more than 4,000 human and animal cell lines used in research worldwide.

Broad Institute of MIT and Harvard

Biomedical Research Institute

Received 2026 AACR Team Science Award for DepMap; poster presented at AACR 2026; awaiting DepMap portal data release for resistance models

A genomics-focused research institute that runs the Cancer Dependency Map (DepMap), the largest open-access effort to map genetic vulnerabilities across cancer cell lines.

AstraZeneca

Pharmaceutical company

Maker of osimertinib (Tagrisso), the drug whose resistance the models replicate

The British-Swedish pharmaceutical company that developed osimertinib (sold as Tagrisso), which generated $7.25 billion in sales in 2025 as the standard of care for EGFR-mutant lung cancer.

Timeline

April 1990 April 2026

10 events Latest: April 22nd, 2026 · 1 month ago

Tap a bar to jump to that date

April 2026
Findings presented at AACR Annual Meeting
Latest Conference

ATCC and Broad researchers presented "Engineering isogenic models harboring resistance mechanisms to the latest-generation EGFR inhibitor in non-small cell lung cancer" at the American Association for Cancer Research meeting in San Diego.
April 22nd, 2026
ATCC and Broad present resistance model poster at AACR 2026
Conference

Researchers presented Poster #7029, "Engineering isogenic models harboring resistance mechanisms to the latest-generation EGFR inhibitor in non-small cell lung cancer," in the Drug Resistance 2: Tyrosine Kinase Inhibitors session at the San Diego Convention Center.
April 22nd, 2026 • 9:00 AM
ATCC and Broad release 13 CRISPR-engineered resistance models
Research Milestone

The collaboration published a panel of isogenic non-small cell lung cancer cell lines, each carrying a single defined resistance mechanism to osimertinib, along with associated genomic datasets available through the DepMap portal.
April 20th, 2026
DepMap team receives AACR Team Science Award
Award

The Broad Institute Cancer Dependency Map team was presented the 2026 AACR Team Science Award in San Diego. Francisca Vazquez delivered the acceptance presentation, reviewing DepMap's history, technological milestones, and computational infrastructure. The portal now serves more than 11,000 users per week across 186 countries.
April 18th, 2026 • 12:30 PM
October 2024
Base editing screens map resistance genetics at scale
Research Milestone

Researchers used CRISPR base editing mutagenesis to prospectively identify genetic mechanisms of resistance to ten oncology drugs across cancer cell lines, demonstrating the feasibility of systematic resistance mapping.
October 1st, 2024
June 2024
Amivantamab-lazertinib beats osimertinib in first-line trial
Clinical

The MARIPOSA trial showed that combining the bispecific antibody amivantamab with the EGFR inhibitor lazertinib extended progression-free survival to 23.7 months versus 16.6 months for osimertinib alone, validating the combination approach to overcoming resistance.
June 1st, 2024
April 2018
Osimertinib becomes first-line standard of care
Regulatory

Based on the FLAURA trial showing nearly doubled progression-free survival compared to older drugs, osimertinib won approval as the preferred first treatment for EGFR-mutant non-small cell lung cancer.
April 18th, 2018
November 2015
FDA approves osimertinib for resistant lung cancer
Regulatory

The Food and Drug Administration granted accelerated approval for AstraZeneca's third-generation EGFR inhibitor, initially for patients whose tumors acquired the T790M resistance mutation on earlier drugs.
November 13th, 2015
March 2012
Cancer Cell Line Encyclopedia profiles 947 lines
Research Milestone

The Broad Institute and Novartis published comprehensive genomic characterization of nearly a thousand cancer cell lines, establishing the molecular foundation for linking genetic features to drug sensitivity.
March 29th, 2012
April 1990
NCI launches the NCI-60 cancer cell line screen
Research Milestone

The National Cancer Institute introduced a standardized panel of 60 human cancer cell lines for drug screening, replacing decades of mouse-based testing and creating the first systematic framework for matching drugs to tumor types.
April 1st, 1990

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

1990–present

NCI-60 Human Tumor Cell Line Screen (1990)

The National Cancer Institute, led by Michael Boyd, replaced three decades of mouse-based drug screening with a panel of 60 human cancer cell lines representing nine tumor types. Over 100,000 compounds were screened through the panel, generating the largest cancer pharmacology database in the world and enabling the COMPARE algorithm for matching drug mechanisms of action.

Then

The panel shifted cancer drug discovery from animal models to human cell-based screening and enabled identification of compounds active against specific tumor types for the first time.

Now

While the NCI-60 did not solve the problem of predicting clinical responses from lab data, it established the conceptual and methodological foundation for all subsequent large-scale cell line panels, including the Cancer Cell Line Encyclopedia and DepMap.

Why this matters now

The ATCC-Broad resistance models represent the next evolutionary step in the same trajectory: from screening compounds against tumors to systematically mapping how tumors defeat those compounds, using increasingly precise genetic tools.

March 2012

Cancer Cell Line Encyclopedia launch (2012)

The Broad Institute and Novartis published comprehensive genomic profiles of 947 cancer cell lines in Nature, cataloging gene expression, chromosomal copy number, and mutations alongside drug response data for 24 compounds. The datasets were made freely available, establishing the molecular foundation for precision oncology research.

Then

Researchers could, for the first time, systematically link specific genetic features in cancer cells to drug sensitivity or resistance at scale, enabling biomarker-driven drug development strategies.

Now

The CCLE became one of the most widely cited resources in cancer biology, directly enabling identification of therapeutic targets such as PRMT5 and WRN. It evolved into the DepMap portal, which now profiles over a thousand cell lines with CRISPR screens and drug sensitivity data.

Why this matters now

The new isogenic resistance models build directly on the CCLE and DepMap infrastructure. Where the CCLE cataloged what cancer cells are, and DepMap mapped what they depend on, the resistance models now catalog how they adapt when those dependencies are targeted.

2001–2006

Imatinib resistance in chronic myeloid leukemia (2001–2006)

After imatinib (Gleevec) transformed chronic myeloid leukemia (CML) from a death sentence into a manageable disease, researchers identified the T315I "gatekeeper" mutation as a key resistance mechanism. This led to the systematic development of second-generation inhibitors dasatinib and nilotinib, and ultimately the third-generation inhibitor ponatinib that overcame the T315I mutation.

Then

Understanding specific resistance mutations enabled rational design of drugs that worked in patients whose tumors had stopped responding to imatinib.

Now

The CML resistance story became the template for precision oncology's approach to drug resistance: identify the molecular escape route, then design a drug to block it. The same logic drove osimertinib's development to overcome T790M resistance in lung cancer.

Why this matters now

The ATCC-Broad models attempt to industrialize for osimertinib resistance what took years of ad hoc research for imatinib resistance. Where CML had one dominant escape route, osimertinib resistance involves at least a dozen, making standardized models essential for systematic study.