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.
The CAP- and CLIA-validated microRNA-371a-3P assay promises earlier detection, fewer CT scans, and more precise treatment decisions for a high-risk patient population.
According to a press release, UC San Diego Health has become the first health system in the United States to offer a clinically validated blood test for testicular cancer. This advance could potentially redefine diagnostic workflows, reduce reliance on imaging, and sharpen treatment decisions for a patient population that often faces both overtreatment and missed recurrences.
The assay, more than a decade in development, measures microRNA-371a-3P, a biomarker shown to detect the presence of testicular cancer cells with about 90% accuracy. Until now, clinicians and clinical laboratories have had limited tools to determine which patients require surgery, chemotherapy, or simply surveillance, especially when imaging is inconclusive.
Testicular cancer strikes roughly 10,000 people annually, primarily men between 18 and 45, yet existing serum markers fail to capture the majority of cases. As a result, laboratories and oncologists have historically struggled with staging uncertainty, unnecessary chemotherapy, and delayed recognition of recurrence. About one-third of patients experience relapses after orchiectomy despite normal CT imaging.
The press release explained that the biomarker’s sensitivity and specificity offer a clearer, earlier signal of active cancer biology—information that can materially change treatment plans.
Further, the test can be used across the care continuum. Before surgery, it can help confirm whether an abnormal testis is malignant and guide surgical decision-making. Post-operatively, it can help determine which patients truly need systemic therapy or further intervention. During surveillance, it may detect recurrence earlier than imaging, allowing less intensive and more precisely timed treatment.
For laboratories, one of the most consequential implications is the potential to reduce the reliance on repeated CT scans, as they carry radiation exposure, cost burdens, and logistical challenges. A validated blood-based alternative, if adopted more widely, could shift surveillance algorithms across health systems.
A Model for Translational Collaboration
The test is currently available for patients at UC San Diego Health and will open to external referrals later this year, allowing outside clinicians and pathology departments to submit samples. It is fully CAP-accredited and CLIA-certified, positioning it for broader adoption by cancer centers seeking higher-resolution molecular insight without expanding imaging capacity.
“This breakthrough represents the kind of investment in innovation that can save lives while improving quality of life for cancer survivors,” said Diane Simeone, MD, director of the Moores Cancer Center at UC San Diego Health. (Photo credit: UC San Diego Health)
For the urology and oncology teams, the test represents years of translational research. For laboratories, it represents a milestone in bringing microRNA-based diagnostics into routine clinical use.
Integrating Results into Multidisciplinary Care
Each test result will feed into UC San Diego Health’s molecular tumor board, a multidisciplinary group that meets every two weeks to review every patient case and interpret biomarker findings in the context of clinical, imaging, and pathological data. For laboratory professionals, this embedded oversight ensures that results are used appropriately and helps refine test performance insights over time.
For labs nationwide, the launch signals a turning point: a real-world, regulated microRNA test with immediate clinical impact—and a template for how laboratory medicine can lead in closing long-standing diagnostic gaps.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
Early detection can raise five-year survival rates above 90%, yet most ovarian cancer cases are found late. Emerging biomarker panels and AI-driven tools are empowering labs to make early diagnosis a reality.
For clinical laboratories, the fight against ovarian cancer highlights both the challenges and opportunities in early disease detection. Despite being one of the most difficult cancers to diagnose in its early stages, ovarian cancer outcomes improve dramatically when it’s caught early—underscoring the importance of laboratory innovation, diagnostic vigilance, and collaboration with clinicians. As researchers explore new biomarkers and AI-assisted tools for earlier, less invasive detection, lab professionals are positioned to play a pivotal role in advancing women’s health and improving survival rates.
Detecting ovarian cancer early is challenging but crucial for timely, effective treatment and improved survival. Too often, women are diagnosed after the disease has advanced. However, experts emphasize that the so-called “silent killer” doesn’t have to be silent—greater awareness of its warning signs and risk factors can make a life-saving difference.
“All women are at risk for gynecologic cancers, and risk increases with age,” explained Ruth Stephenson, DO, Gynecologic Oncologist at RWJBarnabas Health (RWJBH) and Rutgers Cancer Institute in a blog post. “If women suspect something isn’t right, for any reason, they shouldn’t hesitate. Early detection is their greatest asset.”
Stephenson encourages women to be proactive by maintaining regular health visits and being cognizant of their risk factors and the possible symptoms of ovarian cancer.
Other symptoms may include fatigue, upset stomach, back pain, pain during intercourse, constipation, menstrual cycle changes, and abdominal swelling.
Declines in Ovarian Cancer Cases Reflect Prevention Gains but Ongoing Risks Persist
Cases of ovarian cancer have been on the decline over the past several decades and ovarian cancer deaths have decreased by 43% since 1976, mostly due to increased use of oral contraceptives and lower use of hormonal therapies. According to the ACS, approximately 20,890 women will receive an ovarian cancer diagnosis in 2025 and about 12,730 women will die from the disease this year. Approximately half the diagnoses of ovarian cancer occur in women over the age of 63 and it is the sixth most common cancer among women in the US. A woman’s risk of getting the disease is about 1 in 91 and the risk of dying from ovarian cancer is approximately 1 in 143.
The cause of most ovarian cancers is unknown, but several aspects have been identified that may affect the risk for obtaining the illness, including:
Older age
Inherited gene mutations, such as BRCA1, BRCA2, or Lynch syndrome
Ruth Stephenson, DO, Gynecologic Oncologist at RWJBH and Rutgers Cancer Institute noted, “Knowing your family history of ovarian and breast cancers, listening to your body, and asking the right questions are among your strongest tools.”
The five-year survival rate for women diagnosed in Stage 1 of ovarian cancer is over 90%, but the survival rates decrease substantially when diagnosed in the later stages. Researchers have been using AI along with blood tests that combine protein and lipid markers to develop methods for earlier and less invasive detection of the disease. Other studies are being conducted to determine whether urine or vaginal samples can detect molecular changes linked to ovarian cancer.
Awareness Campaigns
In September, the ACS and Break Through Cancer announced a collaboration to advance awareness and prevention of ovarian cancer. “This alliance will turn two decades of scientific advances into action by combining research, education, awareness, marketing, and policy strategies to support those at risk of ovarian cancer and their clinicians,” the ACS said in a news release.
“The Outsmart Ovarian Cancer campaign seeks to close the gap between science and practice to ensure that patients and health care providers know the facts, the options, and have the potential to stop ovarian cancer before it starts,” said William Dahut, MD, chief scientific officer of the American Cancer Society. “This awareness campaign aims to give everyone their best chance to outsmart ovarian cancer.”
Detection and treatment options for ovarian cancer continue to improve and providing women with important information about the disease is part of a fundamental strategy for conquering the illness.
“With the American Cancer Society’s national platform and Break Through Cancer’s scientific engine, we are joining forces to bring this knowledge to millions of women,” said Tyler Jacks, PhD, president of Break Through Cancer. “The Outsmart Ovarian Cancer campaign is poised to share emerging research, inform patients, and support health care providers with resources and evolving prevention strategies.”
As awareness campaigns like Outsmart Ovarian Cancer bring renewed focus to prevention and early diagnosis, laboratories have an opportunity to strengthen their role as educators and innovators. Whether through developing and validating biomarker panels, participating in clinical trials, or helping providers interpret evolving screening data, labs can help bridge the gap between research and real-world care. In the ongoing effort to make ovarian cancer less “silent,” the laboratory’s voice—and its science—are essential.
Despite links to cardiovascular risk, only 0.2% of Americans received an Lp(a) test over the past decade, raising concerns about access, equity, and preparedness for new therapies.
For lab leaders, the findings highlight both the challenges of uneven adoption and the opportunities to drive greater awareness, access, and equity as new therapies approach the market.
The study was published September 26 in Journal of the American College of Cardiology: Advances, used Epic Cosmos, a nationwide database encompassing over 300 million patient records from health systems in all 50 states. It marks the first time Epic Cosmos has been used at this scale within the University of California system, and the first study to assess national patterns of Lp(a) testing at this volume.
Lp(a) is a cholesterol particle in the blood that is almost entirely determined by genetics. Elevated levels, which affect about 20% of the US population, are linked to significantly higher risk of heart attack, stroke, and aortic valve disease. Unlike LDL cholesterol, Lp(a) does not respond to diet or lifestyle changes, and currently there are no widely available therapies to lower it—though several are in late-stage clinical trials.
US Testing Rates Remain Low
An article on the study stated, “They found that between 2015 and 2024, just 728,550 patients, representing only 0.2% of the US population, underwent Lp(a) testing. Testing increased from about 14,000 patients in 2015 to more than 300,000 in 2024, but overall rates remain far below what experts recommend for identifying individuals at risk.”
European nations are moving toward universal Lp(a) screening as a key early predictor of heart disease, while the U.S. continues to lag behind.
“By analyzing national data from over 300 million patients, we’ve uncovered how much work remains to bring Lp(a) testing into routine care,” said Mattheus Ramsis, MD, lead author and assistant professor of medicine at UC San Diego School of Medicine.
Mattheus Ramsis, MD, lead author and assistant professor of medicine at UC San Diego School of Medicine noted, “These insights give us a roadmap for expanding access and addressing gaps. We’re seeing a growing recognition among clinicians of the importance of Lp(a) testing, but the low overall testing rates and regional imbalances highlight how much further we need to go. Broader awareness and access to testing could make the difference between catching disease early and missing an opportunity to prevent heart attacks and strokes, ensuring that all patients benefit from emerging therapies.” (Photo credit: UC San Diego Division of Cardiovascular Medicine)
Testing Patterns
The UC San Diego study found stark inequities in testing patterns. Adults aged 50 to 65 were most likely to be tested, and testing was nearly equal between men and women. But less than 10% of patients tested were Black and only 7% were Hispanic or Latino, despite both groups being disproportionately impacted by cardiovascular disease.
“We’re seeing a growing recognition among clinicians of the importance of Lp(a) testing, but the low overall testing rates and regional imbalances highlight how much further we need to go,” Ramsis said. “Broader awareness and access to testing could make the difference between catching disease early and missing an opportunity to prevent heart attacks and strokes, ensuring that all patients benefit from emerging therapies.”
Geographic disparities also stood out. California, Ohio, and Texas accounted for more than a quarter of all tests nationwide, while some states saw almost no uptake. Researchers say this uneven adoption underscores the need for clearer national guidelines and more consistent payer coverage to make Lp(a) testing accessible everywhere.
The study also noted that there was a shift in how tests are being conducted. The article said, “In 2015, most measurements used older ‘mass-based’ assays, which measure the total weight of Lipoprotein(a) in a blood sample. However, by 2024, two-thirds of tests were performed using the more accurate molar assays, in line with evolving clinical guidelines. Molar assays measure the actual number of Lp(a) particles in a person’s bloodstream to assess cardiovascular disease risk, rather than just the mass of particles.”
Co-author Ehtisham Mahmud, MD, professor of medicine and chief of the Division of Cardiovascular Medicine at UC San Diego, stressed the importance of laboratories in expanding adoption.
Mahmud commented, “The rise in testing is encouraging, but we are still far from where we need to be. If we want to close the gaps in cardiovascular risk assessment, especially in underserved communities, we need broader education, clearer guidelines and consistent insurance coverage for Lp(a) testing.”
For laboratory leaders, one of the most important steps in closing the gap on Lp(a) testing is proactive communication with physicians. Many clinicians may not be fully aware of the latest guidelines recommending at least one lifetime Lp(a) test for adults, or of the shift from mass-based to molar assays that better assess cardiovascular risk.
Lab leaders can play a central role by educating providers on when and why to order the test, sharing local testing capacity, and emphasizing how results may guide risk stratification as new therapies reach the market. By positioning themselves as trusted partners in cardiovascular prevention, labs can help physicians incorporate Lp(a) testing into routine practice, expand access to high-risk patients, and ultimately strengthen patient outcomes.
Fewer than half of patients followed up with a colonoscopy after abnormal blood-based colorectal cancer screening.
A new study from UCLA Health reveals that while blood-based tests for colorectal cancer offer a more convenient screening option, many patients do not complete the critical follow-up colonoscopy needed to confirm abnormal results.
The research, led by investigators at the UCLA Health Jonsson Comprehensive Cancer Center, found that only 49% of patients who received an abnormal blood-based screening result completed a colonoscopy within six months. Over the two-year study period, just 56% of patients ever completed the follow-up procedure.
“Blood-based colorectal cancer screening is promising, but it only works if individuals complete the follow-up colonoscopy,” said Folasade May, MD, PhD, MPhil, associate professor of medicine at the David Geffen School of Medicine at UCLA and senior author of the study. “More efforts are needed to help patients follow through to actually diagnose and treat the disease.”
Follow-Up Gaps Mirror Stool-Based Screening Rates
According to the study, the follow-up rates for blood-based tests were comparable to those observed for stool-based screenings but remain far below the levels considered optimal for timely detection and treatment of colorectal cancer. Colonoscopy is a crucial next step after an abnormal screening result, allowing physicians to confirm the presence of cancer or pre-cancerous polyps.
The study also highlighted disparities related to insurance type and overall health. Patients with Medicare Advantage were significantly less likely to complete a follow-up colonoscopy compared to those with private insurance. Additionally, individuals with fewer health conditions were more likely to pursue timely follow-up care. Race and ethnicity were not significant predictors of follow-up completion in this cohort, in contrast to prior research on stool-based screening.
Colorectal Cancer Screening Remains a Vital Public Health Priority
Colorectal cancer is the second leading cause of cancer-related deaths in the United States among men and women combined. Experts emphasize that early detection through regular screening can save lives. However, many patients avoid screening due to fear, limited access, or challenges with preparation for traditional tests such as colonoscopy or stool-based screening.
Folasade May, MD, PhD, MPhil, associate professor of medicine at the David Geffen School of Medicine at UCLA said, “This study underscores that convenience alone does not ensure early cancer detection. Patients, clinicians, and health systems must work together to ensure that abnormal results lead to timely diagnostic procedures.”
Study Design and Methodology
The researchers conducted a retrospective analysis of medical claims data from more than 6,000 individuals aged 45 and older who received the Shield blood-based colorectal cancer screening test between 2022 and 2024. The analysis focused on 452 patients who received an abnormal result and tracked whether they completed a follow-up colonoscopy within six months.
Timothy Zaki, MD, a senior gastroenterology fellow at UCLA Health and the study’s first author, said the findings provide valuable real-world insight into patient behavior after blood-based screenings. “Understanding how often patients follow through with colonoscopy after an abnormal result is critical to assessing the potential impact of these newer screening methods on colorectal cancer outcomes,” he said.
Implications for Clinical Practice
The study, published in the journal Gastroenterology, emphasizes that timely follow-up is essential to ensure that blood-based screening tests translate into meaningful health benefits. Delays or failures to undergo colonoscopy after an abnormal result can compromise early detection and treatment, reducing the overall effectiveness of screening programs.
May added, “Our findings highlight the need for targeted interventions to improve follow-up rates, particularly among patients with Medicare Advantage or multiple health conditions. These steps are crucial to fully realize the potential of blood-based colorectal cancer screening.”
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.
