Caris Life Sciences' Real-World Data Uncovers Metastatic Breast Cancer Patient Responses and Resistance to Trastuzumab Deruxtecan
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
Key Figures
Market Reality Check
Peers on Argus
CAI gained 0.85% while key biotech peers were mixed: MDGL and HALO were up, MRNA and ROIV were down. Momentum scanner only flagged HALO moving down, suggesting today’s move in CAI is stock-specific.
Historical Context
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Jan 12 | Prelim earnings update | Positive | -10.2% | Preliminary Q4 and FY 2025 results showed rapid revenue and case growth. |
| Jan 12 | MCED partnership | Positive | -10.2% | Everlywell partnership to launch Caris Detect multi‑cancer early detection assay. |
| Jan 05 | Conference appearance | Positive | -2.1% | Planned presentation at J.P. Morgan Healthcare Conference with webcasted remarks and Q&A. |
| Dec 19 | Alliance expansion | Positive | +0.3% | Providence Swedish Cancer Institute joined Caris Precision Oncology Alliance, expanding to 99 centers. |
| Dec 16 | Genentech collaboration | Positive | +3.4% | Multi‑year Genentech deal with eligibility for upfront, milestone payments and royalties. |
Recent history shows several positive announcements followed by negative price reactions, indicating a tendency for good news to see selling pressure.
Over the last few months, Caris reported strong preliminary Q4 and FY 2025 growth, major partnerships (Everlywell for its MCED assay and a multi‑year Genentech collaboration with up to $1.1 billion in potential milestones), and continued network expansion to 99 alliance cancer centers. Despite generally positive operational news, several events saw negative share reactions, so today’s positive scientific publication fits into an ongoing story of rapid platform and data expansion against a volatile trading backdrop.
Market Pulse Summary
This announcement emphasizes Caris’s strength in population‑scale, multiomic real‑world data, analyzing 2,799 T‑DXd–treated metastatic breast cancer patients to uncover resistance mechanisms. It reinforces the value of whole exome and transcriptome sequencing as a differentiating asset for precision medicine and biopharma partnerships. In context of recent earnings growth and collaborations, key watchpoints include how effectively Caris converts such scientific insights into commercial diagnostics, drug discovery deals, and sustained data advantages over time.
Key Terms
multiomic medical
clinico-genomic medical
HER2-positive medical
HER2-low medical
AI-generated analysis. Not financial advice.
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
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
What did Caris (CAI) report on January 28, 2026 about T‑DXd resistance in metastatic breast cancer?
How does ABCC1 expression affect trastuzumab deruxtecan outcomes according to Caris (CAI)?
What role did ERBB2 (HER2) expression play in the Caris (CAI) study of T‑DXd?
Did Caris (CAI) find genetic changes after T‑DXd treatment that indicate acquired resistance?
How many patients were included in the Caris (CAI) real‑world T‑DXd study and what profiling was used?
What implications did Caris (CAI) highlight for biopharma and drug development?
