Category: 8. Health

  • 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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    Keerti Gopal

    Keerti Gopal

    Reporter, Health and Justice

    Keerti Gopal covers intersections between climate change, public health and environmental justice at Inside Climate News. Previously, she covered climate activism and movement repression. She is a National Geographic Explorer and has received fellowships from Fulbright, the Solutions Journalism Network, The Lever, and the National Press Foundation.

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  • Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study | Cardiovascular Diabetology

    Association of prediabetes and insulin resistance on prognosis of patients with moderate-to-severe coronary artery calcification: a prospective cohort study | Cardiovascular Diabetology

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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

    Claim Your CME Credit at

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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.

    Continue Reading

  • Scientists reveal how chemotherapy causes genetic damage in healthy blood

    Scientists reveal how chemotherapy causes genetic damage in healthy blood

    For the first time, scientists have systematically studied the genetic effects of chemotherapy on healthy tissues.

    Researchers from the Wellcome Sanger Institute, the University of Cambridge, Cambridge University Hospitals NHS Foundation Trust (CUH) and their collaborators analysed blood cell genomes from 23 patients of all ages who had been treated with a range of chemotherapies.

    Published today (1 July) in Nature Genetics, the researchers show that many but not all chemotherapy agents cause mutations and premature aging in healthy blood.

    As part of Cancer Grand Challenges team Mutographs, the researchers uncovered new patterns of DNA damage, or mutational signatures, associated with specific chemotherapy drugs.

    The researchers suggest that the damaging genetic effects of chemotherapy identified by whole genome sequencing could guide the future treatment of patients with effective chemotherapies that have less harmful effects on healthy tissues.

    Chemotherapy is a type of anti-cancer treatment that works by killing cancer cells. It is a systemic treatment, meaning it works throughout the body, and can be administered as a single chemotherapy drug or a combination of drugs.1 In developed countries, it is estimated that around 10 per cent of the population has received chemotherapy treatments for cancer and other diseases at some point in their lifetime.2

    Chemotherapy can have long-term side effects on healthy, non-cancerous tissues, and is associated with an increased risk of secondary cancers. However, there is limited understanding of the biological mechanisms underlying these side effects.

    With new genomic technologies, researchers can explore mutations in normal cells and begin to investigate the extent and long-term consequences of DNA damage from chemotherapy on healthy tissues.

    In a new study, scientists set out to research the effects of chemotherapy on healthy blood. The Mutographs team at the Sanger Institute, University of Cambridge, CUH and their collaborators chose to study blood due to its ease in sampling and ability to culture blood in the laboratory. Plus, the numbers of mutations in normal blood are very consistent between people, giving a good baseline to see whether they are higher in individuals who have received chemotherapy.

    The researchers sequenced blood cell genomes from 23 individuals aged three to 80 years, who had been treated with a range of chemotherapies for various blood and solid cancers. Most of the patients were treated at Addenbrooke’s Hospital in Cambridge and had received a combination of chemotherapy drugs. Collectively, they had been exposed to 21 drugs from all of the main chemotherapy classes, including alkylating agents, platinum agents and anti-metabolites. The results were compared with genomic data from nine healthy people who had never received chemotherapy.

    From analysing the whole genome sequence data, the team found that many classes of chemotherapeutics, but not all, do produce higher numbers of mutations in normal blood cells. For example, a three-year-old patient who was treated for neuroblastoma, a cancer of nerve tissue, had more than the number of mutations found in 80-year-olds who had never received chemotherapy.

    By looking at patterns of damage in the DNA, known as mutational signatures, the researchers showed that different chemotherapeutics have different mutational signatures, and identified four new signatures found in chemotherapy-treated patients.

    For instance, the researchers found that some platinum agents, such as carboplatin and cisplatin, caused very high numbers of mutations. Whereas other drugs in the same class, such as oxaliplatin, did not.

    The researchers suggest that if these drugs are used interchangeably in cancer treatment, and assuming they have the same effectiveness, then this sort of genetic information could be incorporated in order to administer chemotherapies with fewer harmful effects.

    The team also made discoveries around the effects of chemotherapy on the population of cells that generate blood, known as hematopoietic stem cells.

    In normal aging, the hematopoietic stem cells producing blood decrease in diversity, due to the expansion of clones of cells that have “driver” mutations in cancer genes. Chemotherapy caused a similar pattern of change, but prematurely in some middle-aged adults. Particularly in children who have had chemotherapy, their blood appeared to prematurely age, which may increase the risk of secondary cancer later in life.

    Scientists suggest that genomic data could help in choosing the chemotherapies for children that minimise this premature aging, and genomic technologies could monitor for further changes later in life.

    Dr Emily Mitchell, first author at the Wellcome Sanger Institute and clinician at CUH, said: “For the first time, we have taken a systematic view of the genetic effects of chemotherapy on healthy tissues – in this case, blood. We find that some, but not all chemotherapies cause genetic mutations and premature aging in normal blood. This study lays the groundwork for future research into the effects of chemotherapy on many other normal tissues, including multiple tissue sampling pre and post treatment, across a range of chemotherapies in a larger group of patients. This comprehensive view would reveal the full range of effects of different chemotherapies, and help us to optimise patient health in the long term.”

    Dr Jyoti Nangalia, co-lead author at the Wellcome Sanger Institute and Consultant Haematologist at CUH, said: “The effects of chemotherapy we see here – increasing numbers of mutations and premature aging of healthy blood – reasonably contribute to the heightened risk of additional cancers and the patient’s ability to tolerate further treatments in the future. Given that for many cancers, chemotherapy drugs can be switched with other agents to achieve similar results, we hope such genomic data will guide the optimisation of future treatment plans to deliver effective chemotherapies with much fewer damaging side effects for patients.”

    This important research helps us better understand how some chemotherapy drugs can affect healthy cells as well as cancer cells. While many cancers can now be targeted using precision therapies, chemotherapy remains a key way to treat some cancers and saves many lives every year, so it’s vital that patients continue with the treatment recommended by their doctor. At the same time, studies like this are crucial for helping scientists improve cancer treatments in the future – making them not only more effective but also safer for people living with cancer.”


    David Scott, Director of Cancer Grand Challenges

    Professor Sir Mike Stratton, Mutographs team lead and co-lead author at the Wellcome Sanger Institute, said: “I believe that the results of this study hold implications for the way that chemotherapies are used to treat cancer patients. We are constantly on the lookout for better ways of giving therapy and minimising the side effects of toxic, systemic treatments. I’m hopeful that the genomic information from this and future studies will guide choices of chemotherapies, and their adoption in clinical practice.”

    Source:

    Wellcome Trust Sanger Institute

    Journal reference:

    Mitchell, E., et al. (2025). The long-term effects of chemotherapy on normal blood cells. Nature Genetics. doi.org/10.1038/s41588-025-02234-x.

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  • Change trackers: New consortium to catalog DNA mutations across human lifetime

    From the time we are conceived and through old age, genetic mutations accumulate in all our tissues, eluding the body’s typically efficient DNA repair machinery and potentially affecting our health and well-being.

    In a new project, a team of researchers from multiple institutions including Yale will catalog these changes, known as somatic mutations, more than two decades since scientists first logged snapshots of 3 billion DNA base pairs that make up the human DNA. The project will focus specifically on mutations across 19 tissue sites in 150 individuals without disease.

    The project, called the Somatic Mosaicism across Human Tissues (SMaHT) Network, and which will include more than 300 researchers, is described today in the journal Nature. 

    “We want to know how many mutations there are in as many tissues of the body we can to understand how our body changes over time,” said Flora Vaccarino, the Harris Professor at the Yale Child Study Center, professor of neuroscience at Yale School of Medicine, and co-corresponding author of the perspective paper.

    There is a general belief that people are born with an immutable set of DNA sequences inherited from their parents that dictate almost all aspects of their biology.  But even a few days after fertilization, cells of the embryo develop somatic mutations which can affect development. In the embryo, mutations of single nucleotides within a cell, known as SNVs (single nucleotide variants), occur at a rate of about one to five SNVs per cell division. These mutations slow after birth to two to 65 SNVs per year, depending on the tissue, and so steadily accumulate in our cells as we age. Larger structural DNA mutations are much less frequent but potentially could have a larger impact.

    (Intriguingly, there are 10 times fewer mutations in germ line cells, the reproductive cells in sexually reproducing organisms, than in other post-conception cells.)

    Most of these somatic mutations have little effect on our health — and some may even be advantageous. Other mutations, however, including those which occur in many forms of cancer, can be life-threatening. While cancer is the most well-known disease associated with somatic mutations, recent studies have linked these mutations to developmental syndromes, neurological diseases and inflammatory disorders.

    However, there is no largescale reference database for mutations in different tissue types in a large general population that is needed to begin understanding their impact on development, aging, and disease.

    For the new project, collaborators will seek to define the prevalence and types of somatic mutations in healthy individuals in order to better identify those which may cause harm.

    “Until we understand what is happening in healthy people, we can’t understand what is happening in disease,” Vaccarino said.

    Specifically, the research consortium will look at somatic mutations in multiple tissue types including in the skin, brain, skeleton, heart, lungs, and blood. Finding these mutations in human tissues, however, is challenging, researchers say.

    “Specific mutations can be present in very small numbers of cells or even single cells, and so detecting them is like looking for a needle in a haystack,” said Tim Coorens, co-lead and co-corresponding author from the Broad Institute of MIT and Harvard and currently a research group leader at the European Bioinformatics Institute in Cambridge, UK.

    To overcome these challenges, the consortium is developing and applying state-of-the-art technological advances including sequencing approaches with ultra-low error rates and sequencing the DNA of single cells. This will allow them to track mutations of single nucleotides within a single cell and, at the same time, to monitor RNA which carry out instructions encoded within the DNA.

    “It is like a super-personal genome overtime,” Vaccarino said.

    Eunjung Alice Lee, of Boston Children’s Hospital and the Broad Institute, and Ji Won Oh, of Yonsei University College of Medicine in Seoul, South Korea, are co-lead authors of the perspective paper.

    The SMaHT Network, which includes more than 300 researchers from more than 50 institutions across the United States, is supported by the National Institutes of Health’s Common Fund.

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  • Researchers Find Immune Pathway in Joint Tissue involved in Early Rheumatoid Arthritis

    Researchers Find Immune Pathway in Joint Tissue involved in Early Rheumatoid Arthritis

    A new study by scientists at the University of Colorado Anschutz Medical Campus reveals that joint tissue from patients with early-stage rheumatoid arthritis often have high levels of a protein called granzyme used by the immune system to attack pathogens.

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