Category: 8. Health

  • AI algorithm identifies patients at risk of sudden cardiac arrest

    AI algorithm identifies patients at risk of sudden cardiac arrest

    An AI algorithm used with MRI data can predict which patients are at risk of sudden cardiac arrest, researchers have reported.

    By analyzing heart imaging results, specifically cardiac MRI, electronic health records, and echocardiograms, the AI algorithm was able to “reveal previously hidden information about a patient’s heart health,” according to a statement released by Johns Hopkins University in Baltimore, at which a team led by Changxin Lai, PhD, conducted the study.

    The findings could not only save lives but also avoid unnecessary medical interventions such as the implantation of defibrillators, said senior author Natalia Trayanova, PhD, in the university statement. The work was published on July 2 in Nature Cardiovascular Research.

    “Currently, we have patients dying in the prime of their life because they aren’t protected and others who are putting up with defibrillators for the rest of their lives with no benefit,” Trayanova said. “We have the ability to predict with very high accuracy whether a patient is at high risk for sudden cardiac death or not.”

    Hypertrophic cardiomyopathy is one of the most common inherited heart diseases, affecting one in every 200 to 500 individuals worldwide, and is a leading cause of sudden cardiac death in young people and athletes, Lai and colleagues noted. Many people with the condition live normal lives, but some are at increased risk for sudden cardiac death — and it’s difficult for doctors to identify these patients.

    Clinical guidelines to find patients most at risk for fatal heart attacks have about a 50% chance of identifying the right ones — “not much better than throwing dice,” Trayanova said. In light of this statistic, the group developed a transformer-based, neural network model called Multimodal AI for ventricular Arrhythmia Risk Stratification (MAARS), using it in a development and validation cohort of 553 patients and another, external cohort of 284 patients. All patients were assessed via traditional clinical guidelines and MR imaging at Johns Hopkins Hospital and Sanger Heart & Vascular Institute in North Carolina.  

    Li and colleagues found that MAARS “significantly outperformed” clinical guidelines across all demographics, showing 89% accuracy for predicting sudden cardiac death across all patients and 93% accuracy for people 40 to 60 years old, which is the population among hypertrophic cardiomyopathy patients most at risk.

    MARRS’ performance compared to other cardiac death risk assessment tools (internal cross-validation)
    Measure ACC and AHA guidelines ESC guideline HCM Risk-SCD Calculator EHR Cardiac imaging report LGE-CMR findings MARRS
    Sensitivity 89% 95% 63% 84% 84% 89% 79%
    Specificity 31% 15% 47% 72% 62% 75% 82%
    Accuracy 54% 50% 55% 77% 72% 81% 80%
    AUROC 0.62 0.54 0.54 0.84 0.8 0.86 0.89
    ACC = American College of Cardiology; AHA = American Heart Association; AUROC = Area under the receiver operating curve; ESC = European Society of Cardiology; EHR = Electronic health record; LGE-CMR = Late gadolinium enhancement cardiac MRI

    “MAARS has the potential to substantially improve clinical decision-making and healthcare delivery for patients with [hypertrophic cardiomyopathy], either directly through future integration with automated data extraction systems or indirectly by serving as a valuable proof of concept for the power of multimodal AI in enhancing personalized patient care,” the investigators wrote.

    Going forward, the team plans to test the new model on more patients and expand the algorithm for use with other types of heart diseases, such as cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy, it said.

    The complete study can be found here.

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  • Bonita Gibson, 113, says potatoes and smiling are keys to long life

    Bonita Gibson, 113, says potatoes and smiling are keys to long life

    What’s older than a blender, penicillin, and the U.S. moon landing? A Michigan woman celebrating her 114th birthday on July 4.

    Bonita Gibson, a resident at Waltonwood Carriage Park just outside of Detroit, is believed to be the oldest living person in Michigan, according to a Waltonwood representative.

    Gibson is part of a small population of supercentenarians in the United States, or someone who is at least 110 years old.

    Other supercentenarians across the country include 114-year-old Naomi Whitehead of Pennsylvania, 114-year-old Mary Harris of Tennessee, and 113-year-old Winnie Felps of Texas, according to the Gerontology Research Group.

    Gibson became the oldest known living person in Michigan after the death of 114-year-old Irene Dunham on May 1, 2022. The Gerontology Research Group validated her age the following year on May 4, 2023, two months shy of her 112th birthday.

    Michigan woman flew for the first time at 100 years old

    Gibson drove until she was 99 years old, and took her first plane ride at the age of 100, flying to San Diego, a lifelong dream of hers, Waltonwood said.

    Gibson told USA TODAY some of the keys to her living such a long life include:

    • Eating potatoes (seemingly a nod to her late husband and the business he worked in)
    • Healthy eating
    • Staying positive and always smiling
    • No smoking or drinking

    Michigan woman survived multiple historical events, spent great deal of her life in Idaho

    Gibson was born on July 4, 1911 in a northwestern Kansas city called Hoxie, according to the Gerontology Research Group. She grew up in rural Missouri, and lived through the Spanish Flu Pandemic. 

    As a child, she survived the mumps, measles, and whooping cough, said a representative for Waltonwood Carriage Park. Most recently, she survived COVID-19 in 2020, making her one of the oldest known survivors of the disease, according to the research group.

    Gibson married Kenneth Gibson, her high school sweetheart, in April 1930 in Oregon, Missouri; the pair married during the Great Depression. The couple lived on a farm at the time.

    “We had chickens and a huge garden and all kinds of fruit trees,” Gibson told CBS Detroit in July 2023. “We had plenty to eat. We just didn’t have any money to spend.”

    They eventually moved to Idaho, where her husband’s relative had a farm. The move is what introduced them to the potato industry.

    “He said Kenny can help me in the field and you can be the cook,” Gibson told CBS Detroit. “I hadn’t cooked a thing in my life.”

    After seven years of marriage, the pair had a son, Kenneth Richard, in January 1937. After that, the couple moved to Newdale, Idaho and later, Idaho Falls as her husband worked as a potato farmer. He later worked as a potato broker until he retired in 1977. He died in 2003.

    After decades in Idaho, a move to Michigan

    At the age of 102, she began living in a nursing home in Canton, Michigan, where her grandson lives. As her grandson was moving her to Michigan, Gibson had a request for him, Waltonwood Executive Director Angie Hanson told McKnight’s Senior Living. 

    “She wanted to ride on the back of his Harley, but he wouldn’t let her,” Hanson said.

    Gibson still speaks to her son, 88-year-old Kenneth Richard, every night. She also has three grandchildren, six great-grandchildren, and 16 great-grandchildren.

    Today, she loves reading and cards, watching “Price is Right” each day, and catching up with her friends at Waltonwood.

    This year, she plans to celebrate her birthday by participating in the downtown Plymouth Fourth of July Parade. There will be a banner announcing her birthday, Waltonwood said.

    As Gibson reflected on her life back in 2023, she recalled being married for over 70 years. She and Kenneth made it a point to enjoy themselves, having the most fun in the 1950s and 1960s, she told CBS Detroit.

    “We would go dancing every Saturday with a group of friends,” she told the outlet.

    When asked what helped to hold their marriage together, she tried to answer from the perspective of her high school sweetheart.

    “I would’ve taken her back home several times, but we didn’t have any money, so we had to stay together,” she said.

    Saleen Martin is a reporter on USA TODAY’s NOW team. She is from Norfolk, Virginia the 757. Email her at sdmartin@usatoday.com.

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  • Uterine Cancer Expected to Rise Significantly Over the Next 25 Years – Inside Precision Medicine

    1. Uterine Cancer Expected to Rise Significantly Over the Next 25 Years  Inside Precision Medicine
    2. Fresh fears as doctors chart explosion in cancer that’s surging more rapidly that colon cancer – food favourite could be to blame  Daily Mail
    3. Study Predicts Uterine Cancer Incidence May Significantly Increase by 2050  American Association for Cancer Research (AACR)
    4. Womb cancer deaths may soar by 98% in next 25 years – and everyday foods in Britain could be to blame  GB News
    5. This already-common cancer — and its deadliness — will significantly increase in the next 25 years: study  New York Post

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  • How to Treat Your Knee Pain Without Drugs or Surgery

    How to Treat Your Knee Pain Without Drugs or Surgery

    More than 70 percent of adults 50 and older say they experience pain in their joints from arthritis. And for many older adults, that pain occurs in the knees.

    But a new study finds that a few simple tools can help tame these aches. When researchers combed through existing studies on nondrug treatments that provide the most relief for knee osteoarthritis, knee braces, water therapy (or water exercise) and traditional exercise came out on top.

    For the study, published June 18 in PLOS One, researchers analyzed 139 randomized control trials spanning 9,644 people with knee osteoarthritis and evaluated 12 nondrug treatments, including laser therapies, ultrasound, water exercise, knee braces, traditional exercise and taping.

    Knee braces were the most effective at lowering pain, improving function and easing stiffness, the researchers found. Hydrotherapy, or water exercise, relieved pain, while traditional workouts improved pain and physical function.

    Finding ways to manage symptoms from a menu of options

    David A. Wang, M.D., a sports medicine physician at the Hospital for Special Surgery in New York, says he isn’t surprised that knee braces, hydrotherapy and exercise were the top performers in the meta-analysis. They all put less pressure on the knee, which can ease pain and improve function, he explains. But just because these therapies ranked high in the research doesn’t mean they will work for everyone.

    “There’s no one-size-fits-all for arthritis,” Wang says.

    It’s important to note that there’s no cure for knee osteoarthritis other than a total knee replacement. For those looking to avoid or delay surgery, all you can do otherwise is manage symptoms, Wang says.

    Many people manage their symptoms by treating their knee pain with medications, such as over-the-counter anti-inflammatories. But the study’s authors note that anti-inflammatory drugs are linked to gastrointestinal and cardiovascular issues in older adults.

    Topical treatments and corticosteroid injections can also help, says Tom Kernozek, a professor and chair of physical therapy at the University of Wisconsin–La Crosse. And working with a physical therapist can improve your knee strength and lead you to tools, such as braces or shoe inserts, that may bring relief.

    Another pivotal intervention: weight loss. A study published in Arthritis & Rheumatology found that for older adults with knee osteoarthritis, losing 1 pound of weight removed 4 pounds of pressure from the knees. 

    “Weight loss is a very important part of osteoarthrosis management,” Wang says. Along with exercise, it gives the “most bang for our buck.” Of course, it can take time to shed pounds, just as it can take time to get stronger from exercise, he adds.

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  • Scientists discover protein that helps lung cancer spread to the brain

    Scientists discover protein that helps lung cancer spread to the brain

    Researchers at McMaster University, Cleveland Clinic and Case Comprehensive Cancer Center have uncovered how a protein long associated with Alzheimer’s disease helps lung cancer spread to the brain – a discovery that offers hope that existing Alzheimer’s drugs could be repurposed in preventing cancer’s spread.

    The study, published in Science Translational Medicine on July 2, 2025, details how the protein (BACE1) is instrumental in the development of brain metastases – tumours that spread to the brain from cancers originating elsewhere in the body – in people with lung cancer. These tumours occur in up to 40 per cent of patients with non-small cell lung cancer.

    “We’ve always associated BACE1 with Alzheimer’s disease, so to find it playing a major role in lung cancer brain metastases is an important discovery,” says senior author Sheila Singh, director of McMaster’s Centre for Discovery in Cancer Research and professor with the Department of Surgery. “It’s a reminder that cancer can hijack biological pathways in ways we don’t yet fully understand.”

    To make the discovery, researchers used a cutting-edge gene activation technique known as a genome-wide in vivo CRISPR activation screen. The technique allowed researchers to systematically activate thousands of genes one by one in lung cancer cells and put the modified cells into mice. When BACE1 was switched on, the cancer cells were far more likely to invade the brain.

    BACE1 has long been linked to Alzheimer’s disease, the most common form of dementia. In people with Alzheimer’s, BACE1 cuts a protein called APP, triggering the formation of sticky plaques in the brain.

    Currently, there are limited therapies available once cancer has spread to the brain. However, researchers say the discovery of BACE1 does offer hope as a drug developed for Alzheimer’s could be repurposed.

    The therapy uses a drug called Verubecestat that blocks BACE1 activity. Researchers found that mice given Verubecestat had fewer and smaller tumours, and also lived longer. The drug had shown promise in Alzheimer’s patients but a Phase 3 clinical trial was discontinued in 2018 after a committee determined it was unlikely that positive benefit/risk could be established.

    “The discovery of BACE1 opens the door to repurposing existing treatments like Verubecestat to potentially prevent or slow the spread of lung cancer to the brain, where treatment options are currently very limited,” Singh says.

    The team say more research is needed to better understand the effectiveness of the therapy in preventing the spread of lung cancer to the brain.

    “This study highlights how interdisciplinary partnerships can lead to breakthroughs in understanding and treating devastating diseases like brain metastases,” said Shideng Bao, a researcher in Cleveland Clinic’s Department of Cancer Biology, a corresponding author on the paper. “By identifying BACE1 as a key player in the spread of lung cancer to the brain, we’ve uncovered a promising new avenue for therapeutic intervention that could ultimately improve outcomes for patients.”

    The Sheila Singh Lab collaborated with Cleveland Clinic and Case Comprehensive Cancer Center on the research. Singh and her colleagues are world leaders in brain cancer research, previously discovering a pathway used by cancer cells to infiltrate the brain, as well as new therapeutic approaches.

    The study was supported by funding from the Boris Family Fund for Brain Metastasis Research, the Canadian Cancer Society, the Canadian Institute of Health Research, the Cancer Research UK Lung Cancer Centre of Excellence the Cleveland Clinic Foundation and Lerner Research Institute, and a Sir Henry Wellcome Fellowship.

     —

    Interested in covering this research?

    • Senior author Sheila Singh, director of McMaster’s Centre for Discovery in Cancer Research and professor with the Department of Surgery, can be reached directly at [email protected].

    For any other information, contact Adam Ward, media relations officer with McMaster University’s Faculty of Health Sciences at [email protected].


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  • NIH Scientists Link Air Pollution and Lung Cancer Mutations in Non-Smokers

    NIH Scientists Link Air Pollution and Lung Cancer Mutations in Non-Smokers

    New findings published Wednesday by the National Cancer Institute link tiny, toxic air pollutants to changes in lung cancer tumors at the genomic level in people who have never smoked. 

    Lung cancer is the leading cause of cancer death in the U.S., and the American Cancer Society reports that more people die of lung cancer every year than of colon, breast and prostate cancers combined. Non-smokers account for 10 to 25 percent of all lung cancer cases globally, but research on its causes in patients who have never smoked is less well established than for their tobacco-using counterparts, said the new study’s senior author, Maria Teresa Landi. 

    “We wanted to design a study to try to define the causes of lung cancer in never smokers so that we could potentially provide some suggestions for the improvement of prevention, early detection, therapy, etc,” Landi said. 

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    In their study, published in the journal Nature, Landi and colleagues from the National Institutes of Health’s NCI and the University of California San Diego analyzed the lung tumors of 871 nonsmokers from 28 locations across four continents. They found that the tumors of patients in highly polluted areas had many more genetic mutations than those in areas with cleaner air, and exhibited a diversity of mutations, including patterns typically found in smokers. 

    The paper is part of a larger project Landi is leading on lung cancer in nonsmokers, called the Sherlock-Lung study. 

    Air pollution is a serious public health hazard growing more dire as climate change brings increased wildfires, drought and extreme heat. The American Lung Association found earlier this year that nearly half of the country is living with dangerous levels of pollution, a drastic rise from last year’s figures. Air pollution is linked to a variety of health harms and was already considered the second leading cause of lung cancer.

    The paper adds to well-established links between particulate air pollution and the disease, particularly in epidemiological research, which deals with patterns of disease at the population level. Wednesday’s study takes a different approach, building on genomic research and zooming in on the tumor level. 

    George Thurston, a professor of medicine and population health at New York University, has been a leading scholar on the impacts of air pollution on human health for decades. 

    The new NIH study, which he was not involved in, could play an important role in determining exactly which kinds of particulate matter impact human health, and how, he said. 

    “It’s environmental detective work,” Thurston said. “These kinds of tools will help us understand better the results we’re getting from epidemiology.”

    Notably, the study found a stronger increase in mutations due to air pollution than from exposure to secondhand tobacco smoke. The authors noted that this gap may have been exacerbated by the unreliability of survey data from patients, who self-report their exposure to secondhand smoke with varying accuracy. 

    “I feel like I’m in the Matrix, and I’m the only one that took the red pill.” I know what’s going on, and everybody else is walking around thinking, ‘This stuff isn’t bad for your health.’”

    — George Thurston, New York University School of Medicine

    Thurston pointed out that although secondhand smoke is also a serious health concern, air pollution from fossil fuels is much more ubiquitous.  

    “We are engulfed in fossil-fuel-burning pollution every single day of our lives, all day long, night and day,” he said. 

    Sometimes, he tracks the air pollution on his commute to work using a portable air monitor to dismaying results, and wonders why more people around him don’t seem equally alarmed.

    “I feel like I’m in the Matrix, and I’m the only one that took the red pill,” he said, referring to the sci-fi movie. “I know what’s going on, and everybody else is walking around thinking, ‘This stuff isn’t bad for your health.’”

    The NIH study looked specifically at patients of European and East Asian descent—mostly in Europe, North America and Asia. Landi said future studies aim to expand focus to include participants from Latin America, Africa and Australia. 

    The paper found some geographic differences in mutations, like the strong presence of a particular gene mutation found almost exclusively in subjects in Taiwan and associated with exposure to aristolochic acid, a plant-based substance used in some forms of traditional medicine. The substance has previously been linked to bladder, liver and kidney cancers, but the authors believe theirs is the first evidence linking it to lung cancer.

    The study adds to recent research on environmental and climate impacts on lung health. A paper published in Nature in March found that global warming may be contributing to dehydration and inflammation in human airways that could exacerbate lung diseases, and suggested that most Americans will face increased risk of airway inflammation by the second half of this century.

    Meanwhile, the federal government is gutting funding for research—including at the NIH—studying the impacts of climate change on health and the disparate effects of pollution along social markers like race and gender.

    The NIH study also comes out just one day after the U.S. Senate voted to pass a reconciliation bill that would axe incentives to cut emissions, provide subsidies for health-harming fossil fuels like coal and simultaneously eliminate health care for millions of lower-income Americans through about $1 trillion in cuts to Medicaid and Affordable Care Act marketplaces. Advocates raising the alarm on the health ramifications of air pollution point to dire consequences as a result of these moves.

    Continued fossil fuel combustion leads to more air pollution, while also spawning weather that exacerbates the problem, resulting in greater health care costs, more illness and more deaths. 

    “Many elements of this bill will make Americans sicker, but the bill will also make it more expensive, if not impossible, for millions of Americans to get health care,” wrote Moms Clean Air Force’s federal policy director, Melody Reis, in a statement. 

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  • The adverse effects of metabolic disorder on left ventricular myocardial mechano-energetic efficiency and dysfunction in ischemic cardiomyopathy: insight from a cardiac MRI study | Cardiovascular Diabetology

    The adverse effects of metabolic disorder on left ventricular myocardial mechano-energetic efficiency and dysfunction in ischemic cardiomyopathy: insight from a cardiac MRI study | Cardiovascular Diabetology

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  • 3 Things You Should Know About Targeting NRG1 and Rare Drivers in Pancreatic Cancer

    3 Things You Should Know About Targeting NRG1 and Rare Drivers in Pancreatic Cancer

    RELEASE DATE: June 1, 2025
    EXPIRATION DATE: June 1, 2026

    LEARNING OBJECTIVES

    Upon successful completion of this activity, you should be better prepared to:

    • Evaluate the role of mutations in NRG1 and other genetic alterations in diagnosis and management.

    • Discuss current guidelines and treatment recommendations for the management of patients with advanced pancreatic cancer.

    • Analyze clinical trial data to inform the selection of emerging therapeutic agents for advanced pancreatic cancer.

    • Apply strategies to optimize molecular testing algorithms using diverse testing modalities in advanced pancreatic cancer.

    Accreditation/Credit Designation

    Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

    Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Acknowledgment of commercial support

    This activity is supported by an educational grant from Partner Therapeutics, Inc.

    Off-label disclosure/disclaimer

    This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this activity is for accredited continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity.

    Instructions for participation/how to receive credit

    1. Read this activity in its entirety.

    2. Go to https://www.gotoper.com/annual-oncology-meeting-25-nrg1-postref to access and complete the posttest.

    3. Answer the evaluation questions.

    4. Request credit using the drop-down menu.

    YOU MAY IMMEDIATELY DOWNLOAD YOUR CERTIFICATE.

    To date, 32 genes have been identified as frequently mutated in pancreatic ductal adenocarcinoma (PDAC).1 However, less than 10% of patients are eligible for an FDA-approved targeted therapy, highlighting the need for the development of novel therapeutics.2 Here are 3 things you should know about molecular testing and personalized strategies in pancreatic cancer.

    1 RNA testing is critical to identify actionable gene fusions in PDAC.

    NCCN guidelines recommend tumor molecular profiling in cases of metastatic PDAC.3 RNA-based next-generation sequencing (NGS) is preferred to DNA-based NGS for detecting fusions in genes like ALK, NRG1, NTRK, ROS1, FGFR2, and RET. These fusions are enriched in the 5% to 10% of patients with KRAS wild-type PDAC, a molecular profile more often found in patients younger than 50 years.4 NGS using tumor tissue is preferred to blood-based assays, according to NCCN guidelines.3 Liquid biopsy can be performed concurrently with tissue testing or used when adequate tissue is unavailable.

    RNA-based NGS can detect structural variants of gene fusions, which may inform the potential efficacy of targeted therapies.5 Since RNA sequencing encompasses only exons after splicing, this technique can overcome the technical challenges of excessive sequencing or misaligned reads when DNA-based NGS is used on genes with long or repetitive introns (Figure 1).6 In a heterogeneous tumor in which the gene fusion is present only in some cells, RNA-based NGS can detect the alteration if it is highly expressed.

    FIGURE 1.RNA-based NGS May Overcome Limitations of DNA-Based Testing6

    2 The first NRG1-targeted therapy is approved for advanced or metastatic PDAC.

    NRG1 fusions are found in approximately 1% of solid tumors, most commonly in patients with mucinous adenocarcinoma of the lung and KRAS wild-type PDAC.7 These altered proteins consist of the EGF-like domain of NRG1 attached to the transmembrane domain of various fusion partners. This construct enables constitutive binding and activation of the HER3 receptor, activating RAS and the MAPK and PI3K signaling pathways.

    Zenocutuzumab is a HER2×HER3 bispecific antibody that inhibits NRG1 binding.8 In the phase 1/2 eNRGy trial (NCT02912949), zenocutuzumab demonstrated an overall response rate (ORR) of 30% (95% CI, 23%-37%) in 158 patients of all tumor types with NRG1 fusions.9 The response rate in 33 patients with PDAC was 42.4% (95% CI, 25.5%-60.8%), including 1 complete response and 13 partial responses (Figure 2).10 The median progression-free survival in the overall population was 6.8 months (95% CI, 5.5-9.1 months).9 The most common treatment-related adverse events (TRAEs) were diarrhea (18%), fatigue (12%), and nausea (11%). Infusion-related reactions occurred in 14% of patients. Based on results from the eNRGy study, zenocutuzumab received accelerated approval from the FDA as a second-line systemic therapy to treat advanced, unresectable, or metastatic PDAC harboring an NRG1 gene fusion.11

    FIGURE 2. Response to an NRG1 Inhibitor in Pancreatic Adenocarcinoma10

    3 Ongoing investigations are evaluating numerous other emerging targets of interest.

    In addition to NRG1 fusions, 38.5% of KRAS wild-type PDAC tumors harbor other genetic alterations, including FGFR2 or FGFR3 fusions, ERBB2 (HER2) amplification, BRAF mutations, and RET fusions.4 Erdafitinib demonstrated an ORR of 30% (95% CI, 24%-36%) in patients of different tumor types harboring FGFR alterations in the single-arm, phase 2 RAGNAR trial (NCT04083976).12 The ORR was 56% in patients with PDAC.

    Combination dabrafenib and trametinib produced an ORR of 38% (95% CI, 22.9%-54.9%) in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAF V600 mutation in the single-arm NCI-MATCH trial subprotocol H (NCT02465060).13 Of the 27 evaluable patients, the 1 patient with PDAC achieved stable disease. Combined use of dabrafenib and trametinib received accelerated approval to treat patients with unresectable or metastatic solid tumors, including PDAC, that harbor BRAF V600E mutations and who have progressed following prior treatment.14

    Selpercatinib yielded an ORR of 43.9% (95% CI, 28.5%-60.3%) in patients with RET fusion-positive non-lung and non-thyroid solid tumors in the phase 1/2 LIBRETTO-001 basket trial (NCT03157128).15 The ORR was 44% in patients with PDAC. Selpercatinib received accelerated approval to treat adults with locally advanced or metastatic solid tumors, including PDAC, that harbor a RET gene fusion and who have progressed following prior treatment.16

    The HER2-targeting antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (T-DXd) has not provided as much benefit in patients with PDAC. In the phase 2 DESTINY-PanTumor02 trial (NCT04482309) in patients with solid tumors overexpressing HER2 (immunohistochemistry [IHC], 3+ or 2+), the ORR was 37.1% (95% CI, 31.3%-43.2%) across all cohorts, but only 4.0% (95% CI, 0.1%-20.4%) in those with PDAC.17 Further investigation would be required to determine why this disease type is particularly resistant to T-DXd, but this agent is still approved for HER2 IHC 3+ PDAC under the tissue agnostic approval.

    The TP53 Y220C mutation is the target of the first-in-class p53 reactivator PC14586.18 In the phase 1 portion of the phase 1/2 PYNNACLE trial (NCT04585750) at the highest dose of PC14586, the ORR was 46.2%. In 6 patients with PDAC, 4 achieved stable disease, and 1 achieved an unconfirmed partial response.

    Claudin18.2 (CLDN18.2) is an emerging actionable target in many cancers, including PDAC.19 Therapeutics with various mechanisms of action are under investigation to exploit this target. IBI389 is a CLDN18.2×CD3 bispecific antibody evaluated in a phase 1 study (NCT05164458) in 64 previously-treated patients with CLDN18.2-positive PDAC.20 The ORR was 30.4% (95% CI, 13.2%-52.9%), and the disease control rate was 69.6% (95% CI, 47.1%-86.8%). TRAEs of grade 3 or greater were reported in 54.7% of patients. Treatment was discontinued in 4.7% of patients due to TRAEs. Cytokine release syndrome is an AE of particular concern with IBI389, with grade 1 or 2 events occurring in 51.6% of patients.

    Zolbetuximab is an anti-CLDN18.2 monoclonal antibody being tested against several tumor types and will be assessed in combination with gemcitabine/nab-paclitaxel (GN) vs GN alone as first-line therapy in patients with metastatic pancreatic cancer in a phase 2 study (NCT03816163).21 The primary end point is overall survival.

    Key References

    4. Singhi AD, George B, Greenbowe JR, et al. Real-time targeted genome profile analysis of pancreatic ductal adenocarcinomas identifies genetic alterations that might be targeted with existing drugs or used as biomarkers. Gastroenterol. 2019;156(8):2242-2253.e4. doi:10.1053/j.gastro.2019.02.037

    6. Davies KD, Aisner DL. Wake up and smell the fusions: single-modality molecular testing misses drivers. Clin Cancer Res. 2019;25(15):4586-4588. doi:10.1158/1078-0432.Ccr-19-1361

    9. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion-positive cancer. N Engl J Med. 2025;392(6):566-576. doi:10.1056/NEJMoa2405008

    For FULL References List, visit https://www.gotoper.com/annual-oncology-meeting-25-nrg1-postref

    CME Posttest Questions

    1 A patient is referred to you with a new diagnosis of metastatic
    pancreatic ductal adenocarcinoma (PDAC) with multiple liver
    metastases. The patient is asymptomatic and has an ECOG perform-
    ance status of 0. Which of the following would be the next best step?

    A. Germline testing for inheritable pathogenic mutations

    B. Germline testing and somatic tissue testing

    C. Somatic tissue testing only

    D. Initiate systemic treatment without further testing

    2 Blockade of which of the following molecules is an active
    treatment approach in tumors with NRG1 fusions?

    A. EGFR

    B. HER3

    C. HER4

    D. NRG1

    3 A patient with metastatic PDAC is referred to you after disease
    progression on FOLFIRINOX. No somatic testing was performed at the time of diagnosis. On further investigation, the tumor has no evidence
    of KRAS mutations but has an ATP1B1-NRG1 fusion. Which of the following therapies would you choose at this time?

    A. Gemcitabine plus nab-paclitaxel

    B. Zenocutuzumab

    C. Zenocutuzumab plus gemcitabine

    D. Clinical trial of an NRG1 antibody

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  • Current Situation: Bird Flu in Dairy Cows | The Transmission

    Current Situation: Bird Flu in Dairy Cows | The Transmission

    CDC On April 1, CDC confirmed one human HPAI A(H5N1) infection in a person with exposure to dairy cows in Texas that were presumed to be infected with the virus. This is thought to be the first instance of likely mammal to human spread of HPAI A(H5N1) virus. In May 2024, CDC began reporting additional, sporadic human cases in people who had exposure to infected dairy cows. That latest human case counts are available at H5N1 Bird Flu: Current Situation Summary.

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