Investigators identified more than 100 proteins linked to inherited cancer risk and dozens of existing drugs that could be repurposed for cancer prevention.
Researchers at Vanderbilt University Medical Center (VUMC) and the University of Calgary have developed a new analytical framework that integrates genomic, proteomic, and electronic health record (EHR) data to uncover proteins linked to cancer risk and to identify existing drugs that may be repurposed for cancer prevention. The approach, described in a study published Dec. 2 in the American Journal of Human Genetics, represents a step toward translating large-scale genetic discoveries into actionable prevention strategies across multiple cancer types.
For clinical laboratory directors, the new framework offers a glimpse of how combined genomic, proteomic, and EHR datasets could soon reshape biomarker discovery and test development.
Genome-wide association studies (GWAS) have already identified hundreds of genetic variants associated with increased cancer risk, particularly for breast, colorectal, and prostate cancers, as well as dozens of variants linked to lung, pancreatic, and ovarian cancers.
However, most of these studies have focused on genetic variation and gene expression rather than the downstream proteins that ultimately drive biological function and are more directly targetable by drugs.
Xingyi Guo, PhD, associate professor of medicine in the Division of Epidemiology at VUMC and a co–senior author of the study said, “Previous research, including our work, has identified hundreds of putative cancer susceptibility genes that could be regulated by these risk variants; however, most dysregulated gene expression has not been thoroughly investigated at the protein level.” (Photo credit: VUMC)
Integrating GWAS and Proteomics to Identify Druggable Cancer Risk Proteins
To bridge that gap, the investigators combined large GWAS datasets for six major cancers—breast, colorectal, lung, ovarian, pancreatic, and prostate—with population-scale proteomics data drawn from more than 75,000 participants. The data came from multiple large cohorts, including the Atherosclerosis Risk in Communities (ARIC) study, deCODE genetics, and the UK Biobank Pharma Proteomics Project. The goal was to identify proteins whose circulating levels are associated with inherited cancer risk.
“To deepen the understanding of causal mechanisms and enhance drug discovery efforts, it is imperative to explore data from transcriptomic to proteomic studies,” said Zhijun Yin, PhD, MS, associate professor of biomedical informatics at VUMC and co–senior author, along with Quan Long, PhD, associate professor of biochemistry and molecular biology at the University of Calgary.
Using this integrated approach, the research team identified 365 proteins associated with cancer risk across the six cancer types studied. Through additional analyses to prioritize the most robust findings, they narrowed this list to 101 risk proteins. Notably, 74 of these proteins had not been previously reported as being linked to cancer susceptibility, highlighting the potential of proteomics to reveal novel biology that may be missed by gene-level analyses alone.
The researchers then evaluated whether these risk proteins could be therapeutically targeted. By systematically annotating the proteins using multiple pharmaceutical and drug-development databases, they assessed whether any were already the targets of approved drugs or agents in clinical testing. This step was designed to identify opportunities for drug repurposing—using existing medications for new preventive indications.
“Traditional drug discovery faces challenges of escalating costs, lengthy timelines, and high failure rates. Drug repurposing is a promising strategy to identify new applications for existing drugs with well-documented characteristics,” Guo said.
Among the 101 prioritized proteins, the investigators identified 36 that were considered druggable and potentially targetable by 404 drugs that are already approved or undergoing clinical trials. Of these, 19 proteins were targeted by drugs currently approved or in development for cancer treatment, suggesting a possible extension of oncology therapeutics into the prevention setting.
EHR-Based Analyses Suggest Reduced Cancer Risk with Certain Approved Drugs
To explore real-world relevance, the team leveraged more than 3.5 million de-identified EHRs from VUMC. Using this data, they conducted simulated clinical trials to examine associations between drug exposure and cancer risk. Several approved medications showed signals consistent with reduced cancer risk. One example highlighted in the study was acetazolamide, a diuretic, which was associated with a reduced risk of colorectal cancer in the EHR-based analyses.
“Our findings offer additional insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention,” Yin said. “It is essential to evaluate the effects of the reported candidate drugs through both in vitro and in vivo assays in future research.”
EHRs are rich in diagnostic data, so there is a clear connection between the researchers’ drug discovery efforts and the information that clinical laboratory test results can provide.
With 300,000 men expected to enroll, researchers hope the trial will redefine prostate cancer screening and reduce preventable late-stage disease.
The UK has launched the £42 million Transform trial, the largest prostate cancer screening study in decades—marking a defining moment for pathology and laboratory leaders tracking the future of population-level diagnostics. Designed to determine the safest and most accurate way to detect the country’s most common male cancer, the trial has already begun recruiting participants through GP invitation letters.
Funded by Prostate Cancer UK and the National Institute for Health and Care Research (NIHR), Transform will evaluate new screening strategies under controlled, invitation-only enrollment. Researchers aim to answer a long-standing challenge in men’s health: how to build a national screening pathway that finds aggressive cancers earlier while minimizing unnecessary interventions and harm.
Moving Beyond PSA Alone
For years, the prostate-specific antigen (PSA) test has been the cornerstone of early prostate cancer detection. It is also widely viewed as inadequate. PSA’s poor specificity leads to false alarms, invasive follow-up procedures, and treatments that can leave men with lifelong side effects. Equally troubling, the test can miss fast-growing, dangerous tumors.
Transform is designed to solve these problems. The trial will evaluate a combined pathway involving rapid MRI, PSA, and a new DNA-based saliva test that analyzes inherited genetic risk. Researchers believe this multi-layered approach might catch more aggressive cancers at an earlier stage while reducing the overdiagnosis that has hampered previous screening efforts.
Chief investigator Professor Hashim Ahmed described the launch as “truly game-changing,” noting that safer, more accurate diagnostics are essential before the UK can adopt a national screening program. “Today marks a pivotal step toward getting the results men urgently need,” he said.
Targeting Those at Highest Risk
The study will recruit men aged 50 to 74, with eligibility extended to Black men starting at age 45. Their risk—double that of white men—makes inclusive trial design essential. Importantly, men cannot volunteer independently; only those who receive an official letter can participate. Still, Prostate Cancer UK is urging every invited individual to strongly consider joining.
Current diagnostic gaps are not hypothetical. They show up in clinics every day. Matthew Hobbs, Prostate Cancer UK’s director of research, said today’s pathways fail on both ends—missing aggressive cancers while overidentifying indolent ones that require no treatment. The result, he said, is a mix of preventable late-stage diagnoses and men undergoing unnecessary interventions.
Matthew Hobbs, Prostate Cancer UK’s director of research noted, “We hear from men who were diagnosed late, whose lives may have been saved if they’d been screened earlier. We also hear from men who live with incontinence or impotence after treatments they may never have needed.” (Photo credit: Prostate Cancer UK)
The Human Consequences
These failures are embodied in patients like Danny Burkey, a 60-year-old former teacher from West Yorkshire. His prostate cancer was diagnosed only after it had already metastasized to his bones. Now terminally ill, he believes earlier screening could have changed everything.
“I think a screening program would be a game changer,” he said. Burkey stressed that with 12,000 men dying early from prostate cancer every year in the UK, screening is “the obvious solution.”
Implications for Pathology and Laboratory Leaders
For pathology and lab teams, Transform provides an early look at what prostate cancer diagnostics may soon demand: risk-stratified testing, high-throughput saliva-based genomics, rapid MRI pathways connected to lab processes, and tighter collaboration between radiology, primary care, and molecular diagnostics. If the trial’s triage model proves successful, laboratories could see increased testing volumes, new workflows, and additional reporting complexity—shifts that would require careful workforce planning and quality assurance frameworks.
As the health system moves closer to evidence that may support population-level screening, laboratory leaders will be central to translating research findings into scalable, accurate, and equitable diagnostic practice. Transform is more than a large trial, it’s an early blueprint for the next phase of prostate cancer detection, one in which pathology and laboratory medicine will be indispensable.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
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.
Drug-resistant infections are outpacing treatments, and WHO says laboratory leaders are vital to protecting antibiotic effectiveness.
For laboratory leaders, the latest WHO report on antimicrobial resistance (AMR) underscores just how critical diagnostic testing, data accuracy, and surveillance capacity have become in the global fight against drug-resistant infections. With one in six bacterial infections now resistant to antibiotics, labs stand on the front lines. They are responsible not only for detecting resistant strains but also for generating the data that informs national and international response strategies.
According to a press release, the “Global antibiotic resistance surveillance report 2025”warns that between 2018 and 2023, “antibiotic resistance rose in over 40% of the pathogen-antibiotic combinations monitored,” with “an average annual increase of 5–15%.”
Data from over 100 countries reported to the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) show that growing resistance to essential antibiotics “poses a growing threat to global health.” For the first time, the report presents “resistance prevalence estimates across 22 antibiotics used to treat infections of the urinary and gastrointestinal tracts, the bloodstream and those used to treat gonorrhea.” It examines eight common bacterial pathogens—Acinetobacter spp., Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae, non-typhoidal Salmonella spp., Shigella spp., Staphylococcus aureus, and Streptococcus pneumoniae—each linked to these major infections.
Resistance Highest in South-East Asia and Eastern Mediterranean
WHO found that the “risk of antibiotic resistance varies across the world.” The highest resistance levels are in the WHO South-East Asian and Eastern Mediterranean Regions, “where 1 in 3 reported infections were resistant.” In the African Region, “1 in 5 infections was resistant.”
According to the report, resistance “is also more common and worsening in places where health systems lack capacity to diagnose or treat bacterial pathogens.”
Tedros Adhanom Ghebreyesus, PhD, WHO director-general noted, “As countries strengthen their AMR surveillance systems, we must use antibiotics responsibly, and make sure everyone has access to the right medicines, quality-assured diagnostics, and vaccines. Our future also depends on strengthening systems to prevent, diagnose and treat infections and on innovating with next-generation antibiotics and rapid point-of-care molecular tests.” (Photo credit: WHO)
Gram-Negative Bacteria Present the Greatest Threat
The WHO report highlights that drug-resistant Gram-negative bacteria are becoming increasingly dangerous worldwide, with the heaviest impact seen in countries least equipped to manage the threat. Among these pathogens, E. coli and K. pneumoniae remain the most common causes of drug-resistant bloodstream infections—serious conditions that can lead to sepsis, organ failure, and death.
Globally, resistance to third-generation cephalosporins—the standard treatment for these infections—has climbed above 40% for E. coli and 55% for K. pneumoniae, and in parts of Africa, it exceeds 70%. Other essential antibiotics, including carbapenems and fluoroquinolones, are also losing effectiveness against E. coli, K. pneumoniae, Salmonella, and Acinetobacter. Once rare, carbapenem resistance is now emerging more frequently, reducing available treatment options and forcing reliance on last-resort antibiotics that are expensive, difficult to obtain, and often unavailable in low- and middle-income countries.
Progress in Surveillance but Major Gaps Remain
Despite these concerning trends, the report noted progress in global surveillance.
“Country participation in GLASS has increased over four-fold, from 25 countries in 2016 to 104 countries in 2023.” However, challenges persist: “48% of countries did not report data to GLASS in 2023,” and “about half of the reporting countries still lacked the systems to generate reliable data.” Many nations facing the highest burden of resistance “lacked the surveillance capacity to assess their antimicrobial resistance (AMR) situation.”
The report links its findings to the “political declaration on AMR adopted at the United Nations General Assembly in 2024,” which set global targets for combating antimicrobial resistance.
The declaration emphasizes strengthening health systems and working with a ‘One Health’ approach coordinating across human health, animal health, and environmental sectors.
WHO is calling on countries to strengthen laboratory systems and build reliable surveillance networks, particularly in underserved regions, to better guide treatment decisions and public health policies. The organization has set a goal for all nations to submit high-quality data on antimicrobial resistance and antibiotic use to the GLASS platform by 2030. Achieving this target will require coordinated efforts to improve data quality, expand geographic coverage, and enhance information sharing. WHO also encourages countries to implement comprehensive strategies to address antimicrobial resistance across all levels of healthcare and to ensure that treatment guidelines and essential medicines lists reflect local resistance trends.
The report is accompanied by expanded digital content available in the WHO’s GLASS dashboard, offering global and regional summaries, country profiles based on unadjusted surveillance coverage and AMR data, and detailed information on antimicrobial use.
With resistance trends worsening across regions, laboratory leaders are pivotal to turning the tide on AMR. Expanding diagnostic capabilities, improving data quality, and sharing timely resistance information will be key to shaping effective treatment guidelines and national policies. By advancing surveillance and stewardship from within the lab, clinical professionals can help preserve the power of antibiotics for future generations.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
New studies show that children and teens are developing long COVID at higher rates—especially after multiple infections. Here’s how clinical labs can play a vital role in identifying at-risk patients and supporting early intervention.
As the healthcare system continues to grapple with the lingering effects of COVID-19, new research is drawing attention to a growing—and often overlooked—population: children and teens with long COVID. For clinical laboratory leaders, these findings underscore the continued importance of SARS-CoV-2 testing, variant monitoring, and post-infection diagnostics in younger patients. Studies reviewed by the Center for Infectious Disease Research and Policy (CIDRAP) and others show that long COVID is not only prevalent in youth but more likely to develop after reinfection. With an estimated one million U.S. children already affected, labs play a critical role in helping clinicians identify and manage post-viral complications while providing data that inform vaccine and reinfection risk strategies.
The pooled results of the studies found that long COVID prevalence was 36% among patients who had become infected with the SARS-CoV-2 infection. The highest prevalence was found in South America, and risk factors included being unvaccinated for the virus, contracting a pre-Omicron variant, and being of the female sex.
Another study analyzed from The Journal of Infectious Diseases focused on the effects of long COVID on adolescents in the summer of 2022. In that study, at least one symptom lasted for four weeks or more for 41% of the respondents who also tested positive for a SARS-CoV-2 infection. Adolescents in the study who tested positive also had increased odds of developing neurological symptoms that lasted three months or longer compared to the adolescents in the study who tested negative for SARS-CoV-2. However, the study also concluded that most symptoms are resolved within three months of infection.
Risk Increases with Multiple Infections
The New York Timesrecently reported that a study published in Lancet Infectious Diseases found that children and teenagers are twice as likely to develop long COVID if they became infected with the virus more than once. The study was a part of the National Institutes of Health’s RECOVER Initiative by examining the records of around 465,000 young people under 21 at 40 United States children’s hospitals.
Over a six-month period, it was found that 1,884 per million young people would develop long COVID after being infected with the virus twice, whereas only 904 per million young people developed long COVID after one infection. The exact numbers of young people with long COVID is not known. However, the Centers for Disease Control and Prevention (CDC) estimates the number stands at about 1 million American children, or 1.3% of the population under 18. A similar trend is seen in adults with long COVID.
These numbers are likely conservative, and the issue of long COVID among youth may be more widespread. According to the same study, tens of thousands of young people in the study were treated for conditions associated with long COVID, such as respiratory symptoms and abdominal pain. Yong Chen, PhD, senior author of the study and professor of Biostatistics at Department of Biostatistics, Epidemiology, and Informatics (DBEI), and a Senior Scholar at Center for Clinical Epidemiology & Biostatistics (CCEB) at the University of Pennsylvania (Penn) Perelman School of Medicine, noted the limitations of the diagnostic code. As quoted by The New York Times, he called the findings a mere “subset of the long COVID.”
Yong Chen, PhD, professor of Biostatistics at DBEI, and a Senior Scholar at CCEB at the University of Pennsylvania (Penn) Perelman School of Medicine said, “Your body really has a memory system and is really going to be hurt from recurrent infection.” (Photo credit: University of Pennsylvania)
Mitigating Risk
Now that we are over five years past the initial worldwide lockdowns, the public has begun to live with significantly less fear–– but the risk remains. “People think that reinfections don’t matter as much and don’t take them seriously,” Chen told Time, “Our primary message is that reinfections still matter, and you should do what you can to avoid reinfection by taking a vaccine or wearing a mask.”
However, the CDC has recently approved recommendations made by Health and Human Services Secretary, Robert F. Kennedy Jr., to remove the blanket recommendation for adults 65 and older to be vaccinated against COVID-19 and recommended that patients between six months and 64 years should discuss with their doctors. Critics of the move warn that these ‘softer’ recommendations may limit insurance coverage of the vaccines.
Clinical laboratory professionals should remain vigilant as research continues to reveal how long COVID affects younger populations. The persistence and variability of post-COVID symptoms highlight the need for continued diagnostic vigilance and testing innovation—not only to confirm infection but to monitor lingering inflammatory, respiratory, or neurological effects. By maintaining awareness of evolving studies and updated guidance from public health agencies, labs can help clinicians identify which patients may be at higher risk for long-term complications. Moreover, laboratory data can support broader efforts to track reinfection patterns, inform vaccine strategies, and guide local health systems in managing the ongoing burden of COVID-related chronic illness.
WHO is developing its first global guidelines on multiplex testing for HIV, hepatitis, and STIs, offering lab leaders a framework to optimize diagnostics, streamline workflows, and lead the shift toward integrated, multi-disease testing.
As diagnostic technologies rapidly evolve and healthcare systems shift toward integrated service delivery, laboratory leaders are at the forefront of implementing efficient, multi-disease testing strategies.
In a landmark move, the World Health Organization (WHO) has convened a Guideline Development Group (GDG) to develop its first-ever evidence-based recommendations on multiplex testing, a method that enables simultaneous detection of HIV, viral hepatitis, and STIs from a single sample. This initiative will establish foundational principles for integration, resource prioritization, and diagnostic efficiency, offering lab professionals critical guidance to shape the future of testing across diseases.
The GDG, comprised of international experts and stakeholders, will provide evidence-based recommendations to support integrated, people-centered diagnostic strategies.
As global health systems shift toward more integrated service delivery, multiplex testing is emerging as a practical tool for increasing diagnostic access, streamlining care, and maximizing limited resources, particularly in low- and middle-income countries, where testing gaps remain significant.
“Access to timely and accurate diagnostic testing is essential for the prevention, detection, and management of HIV, viral hepatitis and STIs,” WHO stated in its announcement. “Multiplex testing has emerged as a promising strategy to improve efficiency, expand testing coverage across diseases, and enhance cost-effectiveness.”
A First-of-Its-Kind Guideline
This is the first WHO guideline to explicitly address multiplex testing using the most up-to-date evidence. While the focus will be on HIV, viral hepatitis, and STIs, the guidelines aim to establish critical principles for integration that can be extended to other disease areas over time.
“This guideline will provide critical principles for integration that drive public health impact and chart the course for further multi-disease testing approaches,” WHO noted.
Photo credit: “World Health Organization Flag” by United States Mission Geneva is licensed under CC BY 2.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/2.0/?ref=openverse.
The GDG will address both provider-based testing and self-testing, recognizing the growing role of community-led and patient-driven diagnostics. Key issues on the agenda include how to prioritize limited testing resources, ensure quality assurance, and optimize public health outcomes through integrated diagnostic models.
Guideline Development Group: Global, Inclusive, Independent
The GDG is composed of members from all WHO regions, selected based on their technical expertise, field experience, and perspectives as either implementers or members of affected communities. Importantly, all members participate in their individual capacities and not as representatives of any affiliated organizations.
“In accordance with WHO guidelines for developing recommendations, the GDG is composed of members from all WHO regions, serving in their individual capacities,” the organization explained. “Members do not receive financial compensation for their contributions to this process.”
The GDG includes program managers, healthcare providers, researchers, and community advocates, reflecting the full spectrum of stakeholders involved in diagnostic service delivery. Their diverse backgrounds are intended to ensure that the guidelines are evidence-informed, practical, and contextually relevant across settings.
A virtual meeting is scheduled for November 4-5, 2025, during which the group will discuss evidence, identify priority recommendations, and finalize key principles around multiplex testing and integration.
WHO Opens Public Comment Period
To promote transparency and inclusivity, WHO has opened a public comment period and is inviting feedback on the composition of the GDG. Stakeholders, organizations, and individuals can review member biographies and submit comments via email to hiv-aids@who.int by September 29, 2025.
The upcoming guideline represents a significant step in advancing integrated diagnostics and expanding access to care, particularly in resource-limited settings. By combining clinical evidence with real-world insights, WHO aims to provide countries and implementers with practical, scalable recommendations that improve testing coverage and disease detection at all levels of the health system.
As testing technologies evolve and the demand for multi-disease platforms grows, this guideline may serve as a blueprint for future diagnostic integration efforts, laying the foundation for efficient, patient-centered, and cost-effective care delivery worldwide.
