Researchers in Singapore unveil a breakthrough RNA strategy that simultaneously silences KRAS mutations and activates immune defenses in hard-to-treat tumors.
As precision oncology moves deeper into RNA-based and immune-modulating therapies, clinical laboratories are finding themselves at the center of a rapidly evolving frontier. New research from Singapore signals just how quickly that future is arriving. In two complementary studies, scientists at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), unveiled a dual-action RNA strategy that targets KRAS—one of cancer’s most stubborn and historically “undruggable” genes—while simultaneously jump-starting the immune system to recognize and attack tumors.
For lab leaders, the findings hint at a coming era in which molecular diagnostics, immune-response markers, and vesicle-based delivery technologies converge in routine care.
Researchers from NUS Medicine, together with collaborators from Nanyang Technological University (NTU), A*STAR, and international partners, focused on KRAS because of its prevalence and difficulty to treat. KRAS mutations lock the gene’s molecular switch in a permanent “on” state, driving constant cell growth and helping tumors hide from immune detection. These mutations appear in more than 90% of pancreatic cancers and are also common in lung and colorectal malignancies. Traditional drug approaches have faltered because the KRAS protein binds its signaling molecules too tightly and lacks accessible pockets for small-molecule inhibitors.
A Dual RNA Strategy to Break KRAS Resistance
To get around these challenges, the team paired two RNA tools: antisense oligonucleotides (ASOs) to silence mutant KRAS and an immunomodulatory RNA (immRNA) to activate RIG-I, an innate immune pathway usually triggered by viral infections. Turning on RIG-I sends an antiviral-like alarm through the cell, prompting immune activation that can help unmask tumor cells. Both RNA agents were delivered using red blood cell–derived extracellular vesicles (RBCEVs), natural carriers that can transport nucleic acid drugs safely and efficiently into tumor tissue.
The first study, published in Theranostics, demonstrated that this ASO–immRNA combination effectively killed KRAS-driven cancer cells in lung, colorectal, and pancreatic models. The therapy blocked oncogenic KRAS activity while converting “cold” tumors—those typically invisible to immune attack—into “hot” tumors that attract immune cells. In laboratory models, the approach reduced tumor burden, improved survival, and spared healthy cells.
Preclinical Progress in Pancreatic Cancer
The second study, appearing in the Journal of Controlled Release, advanced the platform for pancreatic ductal adenocarcinoma (PDAC). PDAC is one of the deadliest human cancers, with a five-year survival rate around 10%. It often spreads throughout the peritoneal cavity, leaving patients with few effective treatment options.
In preclinical models of PDAC with peritoneal metastasis, the dual-RNA therapy markedly suppressed tumor growth, restricted abdominal spread, and extended survival. Importantly, safety testing showed no observable toxicity. Investigators say this strengthens the case for eventual clinical trials and highlights the broader versatility of extracellular vesicles as delivery vehicles across multiple RNA-based modalities.
Associate professor Minh Le, Department of Pharmacology, and Institute for Digital Medicine (WisDM), NUS Medicine noted, “Our EV platform precisely targets mutants, sparing healthy tissue, and synergizes KRAS knockdown with RIG-I activation to unleash interferons, immunogenic cell death, and T-cell memory—halting tumor growth and extending survival without toxicity.” (Photo credit: NUS)
For clinical laboratories, these advances signal more than a scientific milestone—they point to a near future in which labs may need to measure KRAS knockdown, track immune-activation signatures, quantify extracellular vesicle uptake, and support increasingly complex molecular workflows. While the therapy remains in the preclinical phase, the implications are clear: RNA-based therapeutics and EV-mediated delivery are moving quickly toward clinical reality, and laboratories will play a central role in bringing those innovations to patients.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
Abbott has announced a $21 billion deal to acquire Exact Sciences, which could accelerate early cancer detection, expand at-home testing, and reshape the diagnostics landscape globally.
Abbott announced on Nov. 20 that it has entered a definitive agreement to acquire Exact Sciences, a move that would expand its presence in the rapidly growing cancer diagnostics market and potentially reach millions more patients. The deal values Exact Sciences at around $21 billion, with shareholders set to receive $105 per share.
If approved, the acquisition would give Abbott control of one of the most influential diagnostics portfolios in the industry, including Cologuard, Oncotype DX, and a growing lineup of liquid biopsy technologies aimed at earlier cancer detection and more precise treatment guidance. The transaction positions Abbott as a key player in the $60 billion U.S. cancer screening and precision oncology market, one of the fastest-growing sectors in healthcare.
The combination of Abbott’s scale with Exact’s oncology innovations underscores a broader shift in the clinical diagnostics market: prevention, early detection, and home-based testing are rapidly evolving from niche innovation strategies into mainstream commercial imperatives. That is a development that clinical lab professionals and pathologists must watch given Abbott’s interest.
The acquisition is expected to be immediately accretive to Abbott’s revenue growth and gross margins, with Exact projected to generate more than $3 billion in revenue this year and sustain high-teens organic growth.
Abbott Chairman and CEO Robert B. Ford noted, “Exact Sciences’ innovation, its strong brand and customer-focused execution are unrivaled,” Ford said. (Photo credit: Abbott)
Exact Sciences CEO Kevin Conroy echoed the sentiment, calling the acquisition an opportunity to expand earlier detection and broaden access worldwide.
Positioning Screening as Part of Primary Care Services
Industry observers agree the deal has vast implications—whether or not it ultimately closes. Consultant and principal at Natel, Eliad Josephson, described in a post on LinkedIn the moment as “a pivotal shift” for the entire ecosystem. “Diagnostics is on fire with Abbott potentially taking over Exact Sciences,” Josephson wrote in a shared analysis.
Josephson highlighted Exact’s strong at-home screening franchise, anchored by Cologuard, and its strategic fit with Abbott’s global reach and deep ties to primary care. Abbott’s footprint in clinics and retail settings could embed cancer screening more deeply into routine visits, transforming the “front door” of care by making early detection more accessible.
“The ability to shift screening into primary care is huge,” Josephson explained.
He added that if Abbott accelerates adoption of Cologuard and next-generation blood-based screening tests, payer coverage and health system integration could move faster than previously expected, reshaping reimbursement and care pathways.
Beyond the U.S., Abbott’s international presence could propel Exact’s products into new markets far more rapidly than the company could manage alone. With cancer incidence rising globally—affecting more than 20 million people each year—expanding access to early detection tools represents both a commercial opportunity and a major public health imperative.
Navigating Cultural and Operational Hurdles
Still, Josephson cautioned that integration will not be straightforward. He pointed to cultural and operational differences between device-centric organizations like Abbott and lab-centric ones like Exact, as well as regulatory timelines and reimbursement uncertainties.
“Will this be easy? No,” he wrote. “Integrating these models is not easy. But regardless if the deal closes, this moment signals where diagnostics is heading.”
Industry stakeholders—from labs and payers to health systems and investors—will need to reassess how they position themselves in a world where cancer detection is increasingly decentralized, data-driven, and integrated into everyday healthcare.
The deal is expected to close in the second quarter of 2026, pending regulatory and shareholder approvals. If approved, Exact Sciences will operate as an Abbott subsidiary, maintain its Madison, Wisconsin presence, and have CEO Kevin Conroy remain in an advisory role to support the transition.
For now, the industry is watching closely.
As Josephson put it: “Scale matters. Outcomes matter. At-home access matters. Preventive screening is becoming mainstream.”
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
Roche’s SBX technology just helped Broad Clinical Labs set a GUINNESS WORLD RECORD for the fastest DNA sequencing ever.
According to a recent press release, for laboratory leaders tracking the next wave of genomic innovation, Roche’s latest advancements in sequencing technology could signal a major shift in research capabilities. At the 2025 American Society of Human Genetics (ASHG) Annual Meeting, the company unveiled new data and collaborations around its Sequencing by Expansion (SBX) platform—a system designed to deliver faster, longer, and more flexible reads.
This technology’s growing adoption by research institutions suggests it could soon reshape how labs approach complex multiomic analysis, precision oncology, and translational research.
World Record Broken
A highlight of the 2025 ASHG Annual Meeting was the GUINNESS WORLD RECORD achievement by Broad Clinical Labs, which used SBX to complete the fastest human genome sequencing to date, processing a sample from DNA extraction to final variant call file in under four hours. This record, achieved in collaboration with Roche Sequencing Solutions and Boston Children’s Hospital, surpassed the previous mark of just over five hours, demonstrating SBX’s ability to deliver rapid, high-quality results.
Mark Kokoris, inventor of the SBX chemistry and head of SBX Technology at Roche commented, “Breaking the GUINNESS WORLD RECORD is a remarkable achievement.” (Photo credit: Roche)
Roche also announced a new collaboration with the Wellcome Sanger Institute, which will conduct multi-project evaluations of SBX across applications such as Bulk RNA sequencing, where longer reads and higher throughput could uncover complex features like spliced isoforms. This partnership adds to a growing network of collaborations that include the Hartwig Medical Foundation, Genentech, The University of Tokyo, and the Broad Institute, reflecting widespread scientific interest in applying SBX across diverse research domains.
Further innovations include progress in methylation mapping using SBX-Duplex, which reads both DNA strands simultaneously, paired with TET-assisted pyridine borane sequencing (TAPS) from Watchmaker Genomics. This workflow enhances accuracy in detecting DNA methylation and holds promise for applications such as liquid biopsy-based cancer detection and novel biomarker discovery.
In another collaboration, researchers at the University of Tokyo leveraged SBX’s speed and flexibility for spatial sequencing of lung cancer tissue, achieving roughly 15 billion reads in just one hour. Roche also presented a target enrichment method using the SBX-Simplex workflow, which employs Unique Molecular Identifiers (UMIs) to generate highly accurate reads from minimal input, an approach that could be particularly valuable in oncology research requiring deep sequencing coverage.
For diagnostics and research laboratories, Roche’s progress with SBX represents more than a technical milestone, it points to new operational opportunities. Potentially faster turnaround times, deeper insights across multiple molecular layers, and improved workflows could help labs expand their research portfolios and strengthen partnerships in precision medicine. As sequencing continues to evolve from discovery to real-world application, forward-thinking lab leaders will want to keep an eye on how SBX’s scalability and speed might redefine their own genomic testing strategies.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
The new Plasma Immuno Prediction Score achieves 96% accuracy in forecasting TNBC outcomes, offering laboratories a powerful tool for precision oncology.
For laboratory professionals, the latest findings in plasma proteomics underscore how the clinical laboratory is becoming central to guiding cancer treatment decisions. The discovery of blood-based protein signatures that can predict immunotherapy outcomes in triple-negative breast cancer (TNBC) demonstrates how lab-developed tests and biomarker assays can directly influence patient care, moving precision oncology forward.
A news release explained that a team of researchers in China has identified a set of plasma proteins that can reliably predict whether patients with TNBC will respond to immunotherapy, potentially transforming treatment strategies for one of the most aggressive forms of breast cancer.
They found that three proteins in particular—arginase 1 (ARG1), nitric oxide synthase 3 (NOS3), and CD28—were strongly linked to treatment outcomes. From this, the team developed a predictive model called the Plasma Immuno Prediction Score (PIPscore), which achieved nearly 86% accuracy in forecasting responses.
“This study transforms how we approach TNBC immunotherapy,” said Yizhou Jiang, MD, co-corresponding author. “By translating complex plasma proteomics into a practical score, we’ve bridged the gap between research and clinical utility.”
Breaking the Bottleneck in TNBC
Triple-negative breast cancer accounts for about 15% of breast cancer cases worldwide and is notoriously difficult to treat because it lacks the hormonal and HER2 targets used in other subtypes. Immunotherapy has emerged as a promising option, but predicting which patients will benefit remains a challenge.
Currently, clinicians rely on biomarkers like PD-L1 expression or tumor mutational burden. However, these markers often fail to capture the complexity of immune responses, leaving doctors without reliable tools to guide decisions. Tumor biopsies, another option, are invasive and impractical for frequent monitoring.
Yizhou Jiang, MD, Fudan University Shanghai Cancer Center, Fudan University, said “Plasma proteomics provides a non-invasive window into systemic immunity. Our work shows that the blood can tell us as much, if not more, than the tumor itself about how a patient will respond.”
How the Study Worked
The research team analyzed dynamic changes in plasma proteins over the course of immunotherapy. Patients who responded to treatment showed sharp rises in immune-activating proteins such as CXCL9 and interferon-gamma (IFN-γ). Those who achieved a pathologic complete response (pCR)—meaning no detectable cancer remained after treatment—had higher levels of ARG1 and CD28, but lower levels of NOS3.
According to the study, these proteins appear to regulate critical aspects of immune activation and tumor suppression. Elevated NOS3, for example, correlated with fewer CD8+ T cells in tumors, suggesting an immunosuppressive role. In contrast, ARG1’s role in arginine metabolism may boost T-cell function and strengthen immune attack on tumors.
To integrate these findings, the researchers developed the PIPscore, a composite of six proteins including ARG1, NOS3, and IL-18. This model stratified patients into high- and low-response groups with impressive precision. The area under the curve (AUC)—a common measure of predictive performance—was 0.858, indicating strong accuracy.
Perhaps most strikingly, the PIPscore predicted 12-month progression-free survival with 96% accuracy, highlighting its potential clinical value.
Linking Blood to Tumor Biology
To strengthen their conclusions, the team also used single-cell RNA sequencing to link blood protein signatures with changes in the tumor microenvironment. For example, patients with higher NOS3 levels showed reduced infiltration of CD8+ T cells into tumors, aligning blood-based findings with tissue-level biology.
“This dual approach—measuring proteins in the blood and validating them against the tumor microenvironment—offers a holistic view of how immunotherapy works,” Jiang said. “It underscores that systemic immunity, not just local tumor factors, dictates treatment success.”
Clinical Implications
The potential benefits of this approach are wide-ranging. Oncologists could use the PIPscore to determine upfront whether a TNBC patient is likely to respond to immunotherapy, sparing non-responders from ineffective treatments, unnecessary side effects, and high costs. Because the test is blood-based, it could be repeated over time, allowing clinicians to adjust treatment plans in real time.
“The PIPscore not only predicts response but also opens doors to targeting metabolic pathways like arginine deprivation to overcome resistance,” Jiang noted. “These findings underscore the importance of systemic immunity.”
Beyond TNBC, the researchers believe the method could be applied to other cancers where immunotherapy outcomes are highly variable.
In addition to plasma proteomics, the field of pharmacogenomics offers another layer of precision in cancer care by examining how genetic variations influence drug response.
When combined with tools like the PIPscore, pharmacogenomic profiling could help oncologists tailor both immunotherapy and supportive treatments to individual patients. For laboratory professionals, this integration underscores the expanding role of molecular diagnostics in personalizing therapy—ensuring patients not only receive the right drug but also the right dosage based on their genetic and immune profiles.
Next Steps
The study’s authors acknowledge that further validation is needed before the PIPscore can enter routine clinical practice. Larger, multi-center trials will be necessary to confirm its reliability across diverse patient populations. Still, experts view the findings as a major step toward more precise cancer care.
As immunotherapy adoption grows, laboratory professionals will be essential in validating, standardizing, and implementing predictive tools like the PIPscore in clinical practice. Their expertise in assay development, quality control, and biomarker interpretation ensures that discoveries at the research level can be reliably translated into real-world diagnostics, ultimately improving outcomes for patients with aggressive cancers like TNBC.
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
