Caris Life Sciences' Real-World Data Uncovers Metastatic Breast Cancer Patient Responses and Resistance to Trastuzumab Deruxtecan

Caris Life Sciences (NASDAQ: CAI) published a large real-world multiomic study (Jan 28, 2026) analyzing 2,799 trastuzumab deruxtecan (T‑DXd)–treated metastatic breast cancer patients.

Rhea-AI Summary

Caris Life Sciences (NASDAQ: CAI) published a large real-world multiomic study (Jan 28, 2026) analyzing 2,799 trastuzumab deruxtecan (T‑DXd)–treated metastatic breast cancer patients. Whole transcriptome sequencing identified ERBB2 (HER2) and ABCC1 as the strongest transcriptomic predictors of T‑DXd–specific overall survival.

Higher ERBB2 expression aligned with better outcomes; higher ABCC1 correlated with poorer outcomes and increased post‑treatment, alongside enrichment of mutations in ERBB2, NFE2L2, KEAP1 and TOP1, suggesting evolving resistance pathways and actionable insights for drug development.

Positive

• Population-scale analysis of 2,799 T‑DXd patients
• WTS identified ERBB2 and ABCC1 as top predictors of survival
• Higher ERBB2 expression linked to improved T‑DXd outcomes
• Preclinical models support ABCC1 role in drug efflux resistance

Negative

• Resistance to T‑DXd is common across treated patients
• Post‑treatment enrichment of mutations (ERBB2, NFE2L2, KEAP1, TOP1) suggests acquired resistance
• ABCC1 expression associated with poorer outcomes, potentially limiting T‑DXd durability

Argus Jan 28 session

+1.88% close to close Open Argus

Details

News Market Reaction – CAI

On Jan 28, the day this news came out, CAI closed 1.88% above the previous close.

Data tracked by StockTitan Argus for the Jan 28 session.

Market Context

This announcement highlights Caris’s ability to leverage population-scale, multiomic real-world data...

Analysis

This announcement highlights Caris’s ability to leverage population-scale, multiomic real-world data in 2,799 T-DXd–treated metastatic breast cancer patients to uncover resistance mechanisms and survival predictors. It reinforces the company’s AI-driven clinico-genomic platform and complements recent earnings growth and collaborations. Investors may focus on how insights like ERBB2 and ABCC1 stratification translate into future biopharma partnerships, diagnostic offerings, and continued evidence generation from the Caris data asset.

Key Figures

Patient cohort size: 2,799 patients

Patient cohort size

2,799 patients

Real-world T-DXd–treated metastatic breast cancer analysis

Historical Context

5 past events · Latest: Jan 12

5 events

1. Jan 12

   Prelim 2025 results

   24h Move

   -10.2%

   Strong Q4 and 2025 revenue growth from molecular profiling and case volumes.

2. Jan 12

   MCED partnership

   24h Move

   -10.2%

   Everlywell partnership to launch Caris Detect multi-cancer early detection assay.

3. Jan 05

   JPM conference

   24h Move

   -2.1%

   Participation and presentation at the 44th J.P. Morgan Healthcare Conference.

4. Dec 19

   Alliance expansion

   24h Move

   +0.3%

   Providence Swedish Cancer Institute joined the Caris Precision Oncology Alliance.

5. Dec 16

   Genentech collaboration

   24h Move

   +3.4%

   Multi-year Genentech deal with eligibility for milestones and royalties.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Key Terms

trastuzumab deruxtecan, t-dxd, her2-positive, her2-low, +2 more

6 terms

trastuzumab deruxtecan medical

"mechanisms of resistance to trastuzumab deruxtecan (T-DXd) in metastatic breast cancer"

A targeted cancer medicine that combines an antibody with a potent chemotherapy payload to seek out and kill tumor cells that express the HER2 protein; think of it as a guided missile that binds a specific cancer marker and delivers the toxic agent directly to the tumor. It matters to investors because regulatory approvals, clinical trial results, safety profile, patent protection and competition directly affect potential sales, company valuations and the outlook for related drug pipelines.

t-dxd medical

"resistance to trastuzumab deruxtecan (T-DXd) in metastatic breast cancer"

t‑dxd is a targeted cancer medicine made of an antibody linked to a powerful chemotherapy drug that homes in on cells with the HER2 protein and delivers the toxic payload directly to them. Investors watch t‑dxd because clinical trial results, regulatory approvals, safety findings, and pricing determine how widely it can be used and how much revenue it could generate—think of it as a precision-guided missile whose market value depends on performance and permission to sell.

her2-positive medical

"approved by the FDA for HER2-positive and HER2-low metastatic breast cancer"

HER2-positive describes cancer cells that have too many copies of the HER2 gene or make too much of the HER2 protein, which acts like an overactive growth switch that drives tumor growth. For investors, HER2 status matters because it determines whether patients can receive specific, often expensive targeted therapies and diagnostic tests, so trial results, approvals, or competing drugs tied to HER2 can strongly affect drug sales and company value.

her2-low medical

"approved by the FDA for HER2-positive and HER2-low metastatic breast cancer"

HER2-low describes a level of the HER2 protein found on certain cancer cells that is detectable but lower than levels historically classified as HER2-positive. Think of it like a dimmer switch rather than an on/off light; it matters to investors because patients in this middle category may become eligible for newer targeted drugs and clinical trials, which can expand market size, affect approval decisions, and change revenue prospects for drug developers.

antibody–drug conjugate medical

"T–DXd, an antibody–drug conjugate approved by the FDA for HER2-positive"

A antibody–drug conjugate is a targeted cancer medicine made by attaching a powerful cell-killing drug to an antibody that seeks out specific markers on diseased cells. Think of it as a guided delivery system that aims to bring toxic therapy directly to bad cells while sparing healthy tissue. Investors care because these drugs can offer higher effectiveness and premium pricing if approved, but they also carry technical, manufacturing and regulatory risks that can swing company value.

multiomic profiling medical

"Caris's comprehensive multiomic profiling, Caris scientists uncovered clinically relevant"

Multiomic profiling is the coordinated measurement of different layers of biological information — for example genes, proteins and small molecules — from the same patient sample to create a more complete picture of how a disease works. For investors it matters because that richer picture can reveal clearer drug targets, diagnostic markers, or patient groups, helping companies prioritize research, reduce development risk and potentially speed more reliable products to market, much like combining several camera lenses to get a sharper image.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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IRVING, Texas, Jan. 28, 2026 /PRNewswire/ -- Caris Life Sciences® (NASDAQ: CAI), a leading, patient-centric, next-generation AI TechBio company and precision medicine pioneer, has published a study in Nature's npj Breast Cancer journal titled, "Mechanisms of Resistance to Trastuzumab Deruxtecan in Breast Cancer Elucidated by Multiomic Molecular Profiling." Utilizing large-scale real-world clinico-genomic data and Caris's comprehensive multiomic profiling, Caris scientists uncovered clinically relevant mechanisms of resistance to trastuzumab deruxtecan (T-DXd) in metastatic breast cancer. This study explains why patient responses vary and reveals how resistance can evolve over time.

This study addresses a critical gap in understanding why responses to T–DXd, an antibody–drug conjugate approved by the FDA for HER2-positive and HER2-low metastatic breast cancer, vary widely since resistance to T–DXd is common. By combining large-scale, real-world clinical outcomes with Caris's comprehensive molecular profiling, including whole exome sequencing (WES) and whole transcriptome sequencing (WTS), the study enables a population-level analysis of resistance pathways across DNA, RNA and protein expression.

"In this large real-world analysis, clinical outcomes allowed Caris to pinpoint molecular features linked to treatment-specific survival," said George W. Sledge, Jr., MD, Caris EVP and Chief Medical Officer. "Post–treatment molecular shifts further reveal biologically plausible routes to acquired resistance, underscoring that RNA–level and multiomic profiling can provide actionable insights beyond standard HER2 classification to better stratify patients and inform therapies." 

The study analyzed 2,799 T–DXd–treated breast cancer patients and found that WTS identified ERBB2 (HER2) and ABCC1 as the strongest transcriptomic predictors of T–DXd–specific overall survival. Higher ERBB2 expression correlated with improved outcomes, while higher ABCC1 correlated with poorer outcomes, independent of HER2 category.

ABCC1 further stratified outcomes within HER2–defined subgroups, indicating predictive value beyond standard HER2 testing and post–treatment samples showed increased ABCC1 expression alongside enrichment of mutations in ERBB2, NFE2L2, KEAP1 and TOP1. Consistent with acquired resistance mechanisms. Preclinical models supported a functional, context–dependent role for ABCC1–mediated drug efflux in T–DXd resistance.

"This study demonstrates how population–scale, multiomic real–world data can drive high impact translational discoveries, reinforcing the value proposition for patients and equipping biopharma with actionable insights into resistance biology to guide next–generation drug development," said David Spetzler, MS, PhD, MBA, Caris President.

About Caris Life Sciences
Caris Life Sciences® (Caris) is a leading, patient-centric, next-generation AI TechBio company and precision medicine pioneer that is actively developing and commercializing innovative solutions to transform healthcare. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms at scale, Caris has created the large-scale, multimodal clinico-genomic database and computing capability needed to analyze and further unravel the molecular complexity of disease. This convergence of next-generation sequencing, AI and machine learning technologies, and high-performance computing provides a differentiated platform to develop the latest generation of advanced precision medicine diagnostic solutions for early detection, diagnosis, monitoring, therapy selection and drug development. 

Caris was founded with a vision to realize the potential of precision medicine in order to improve the human condition. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Cambridge (MA), Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S. and other international markets. 

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the federal securities laws. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding our business, solutions, plans, objectives, goals, industry trends, financial outlook and guidance. In some cases forward-looking statements can be identified by words such as "may," "will," "should," "would," "expect," "plan," "anticipate," "could," "intend," "target," "project," "potential," "contemplate," "believe," "estimate," "predict," "potential" or "continue" or similar expressions. 

You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in these forward-looking statements are reasonable based on information currently available to us, we cannot guarantee that the future results, discoveries, levels of activity, performance or events and circumstances reflected in forward-looking statements will be achieved or occur. Forward-looking statements involve known and unknown risks and uncertainties, some of which are beyond our control. Risks and uncertainties that could cause our actual results to differ materially from those indicated or implied by the forward-looking statements in this press release include, among other things: developments in the precision medicine industry; our future financial performance, results of operations or other operational results or metrics; development, analytical and clinical validation, timing and performance of future solutions by us and our competitors; commercial market acceptance for our solutions, including acceptance of preventive as well as diagnostic testing paradigms, and our ability to meet resulting demand; the rapidly evolving competitive environment in which we operate; third-party payer reimbursement and coverage decisions related to our solutions; risks related to data management, storage, and processing capabilities and our ability to integrate and deploy artificial intelligence and advanced data analytics technologies; our ability to protect and enhance our intellectual property; regulatory requirements, decisions or approvals (including the timing and conditions thereof) related to our solutions; reliance on third-party suppliers; risks related to data security, patient privacy, and compliance with healthcare data protection regulations as well as potential cybersecurity threats to our data platforms; our compliance with laws and regulations; the outcome of government investigations and litigation; risks related to our indebtedness; and our ability to hire and retain key personnel as well as risks, uncertainties, and other factors described in the section titled "Risk Factors" and elsewhere in our Quarterly Report on Form 10-Q filed on or about November 5, 2025, and in our other filings we make with the SEC from time to time. We undertake no obligation to update any forward-looking statements to reflect changes in events, circumstances or our beliefs after the date of this press release, except as required by law. 

Caris Life Sciences Media:
Corporate Communications
CorpComm@CarisLS.com
214.294.5606

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SOURCE Caris Life Sciences

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Caris (CAI) report on January 28, 2026 about T‑DXd resistance in metastatic breast cancer?

Caris reported a multiomic real‑world study analyzing 2,799 T‑DXd–treated patients that identified transcriptomic predictors of survival. According to Caris, WTS highlighted ERBB2 (better outcomes) and ABCC1 (worse outcomes), revealing evolving resistance pathways.

How does ABCC1 expression affect trastuzumab deruxtecan outcomes according to Caris (CAI)?

Higher ABCC1 expression correlated with poorer T‑DXd–specific overall survival in the study cohort. According to Caris, ABCC1 further stratified outcomes within HER2 subgroups and increased post‑treatment, supporting a drug‑efflux resistance mechanism.

What role did ERBB2 (HER2) expression play in the Caris (CAI) study of T‑DXd?

Higher ERBB2 transcript expression correlated with improved T‑DXd outcomes in the real‑world analysis. According to Caris, ERBB2 was one of the strongest transcriptomic predictors of treatment‑specific overall survival by WTS.

Did Caris (CAI) find genetic changes after T‑DXd treatment that indicate acquired resistance?

Yes; post‑treatment samples showed increased ABCC1 expression and enrichment of mutations in ERBB2, NFE2L2, KEAP1 and TOP1. According to Caris, these shifts point to biologically plausible routes to acquired resistance.

How many patients were included in the Caris (CAI) real‑world T‑DXd study and what profiling was used?

The study analyzed 2,799 T‑DXd–treated metastatic breast cancer patients using multiomic profiling including whole exome and whole transcriptome sequencing. According to Caris, this enabled population‑level analysis across DNA, RNA and protein expression.

What implications did Caris (CAI) highlight for biopharma and drug development?

Caris said population‑scale multiomic real‑world data can provide actionable insights into resistance biology to guide next‑generation drug development. According to Caris, these findings may inform stratification and new therapeutic strategies.