Latest news with #drugResistance
Yahoo
10-07-2025
- Health
- Yahoo
Fungal infections are getting harder to treat
Fungal infections are getting harder to treat as they grow more resistant to available drugs, according to research published Wednesday in The Lancet Microbe. The study focused on infections caused by Aspergillus fumigatus, a fungus that is ubiquitous in soil and decaying matter around the world. Aspergillus spores are inhaled all the time, usually without causing any problems. But in people who are immunocompromised or who have underlying lung conditions, Aspergillus can be dangerous. The fungus is one of the World Health Organization's top concerns on its list of priority fungi, which notes that death rates for people with drug-resistant Aspergillus infections range from 47%-88%. The new study found that the fungus' drug resistance is increasing. On top of that, patients are typically infected with multiple strains of the fungus, sometimes with different resistance genes. 'This presents treatment issues,' said the study's co-author, Jochem Buil, a microbiologist at Radboud University Medical Centre in the Netherlands. Buil and his team analyzed more than 12,600 samples of Aspergillus fumigatus taken from the lungs of patients in Dutch hospitals over the last 30 years. Of them, about 2,000 harbored mutations associated with resistance to azoles, the class of antifungals used to treat the infections. Most of them had one of two well-known mutations, but 17% had variations of the mutations. Nearly 60 people had invasive infections — meaning the fungi spread from the lungs to other parts of the body — 13 of which were azole-resistant. In those people, nearly 86% were infected with multiple strains of the fungi, making treatment even more complicated. 'It is an increasingly complicated story and physicians may have trouble identifying whether or not they are dealing with a drug-resistant fungal infection,' said Dr. Arturo Casadevall, chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, who wasn't involved with the research. Before treating an Aspergillus fungal infection, doctors look for resistance genes that can give them clues about which drugs will work best. If someone is infected with multiple strains of the same type of fungus, this becomes much less clear-cut. Oftentimes, different strains will respond to different drugs. 'Azoles are the first line of treatment for azole-susceptible strains, but they do not work when a strain is resistant. For those, we need to use different drugs that don't work as well and have worse side effects,' Buil said, adding that some people will require treatment with multiple antifungal drugs at the same time. The findings illustrate a larger trend of growing pressure on the few drugs available to treat fungal infections — there are only three major classes of antifungal drugs, including azoles, that treat invasive infections, compared with several dozen classes of antibiotics. Resistance to such drugs is growing, and new ones are uniquely difficult to develop. Humans and fungi share about half of their DNA, meaning we're much more closely related to fungi than we are to bacteria and viruses. Many of the proteins that are essential for fungi to survive are also essential for human cells, leaving fewer safe targets for antifungal drugs to attack. 'The big problem for all of these fungal species is that we don't have a lot of antifungals,' said Jarrod Fortwendel, a professor of clinical pharmacy at the University of Tennessee Health Science Center, who was not involved with the research. 'Typically the genetic mutations that cause resistance don't cause resistance to one of the drugs, it's all of them, so you lose the entire class of drugs.' Further complicating matters, the vast majority of azole resistance in Aspergillus fumigatus stems from agriculture, which widely uses fungicides. The fungicides typically have the same molecular targets as antifungal drugs. Farmers spray them on crops, including wheat and barley in the U.S., to prevent or treat fungal disease. (The first instance of azole resistance was documented in the Netherlands, where antifungals are widely used on tulips.) Aspergillus fungi aren't the target, but exposure to the fungicides gives them a head start developing genes that are resistant to the targets, sometimes before an antifungal drug with the same target even hits the market. This was the source of the vast majority of the drug resistance analyzed in the study. Fortwendel noted that fungal resistance is increasingly found around the world. 'Basically everywhere we look for drug-resistant isotopes, we find them,' he said. 'We are seeing this azole drug-resistance happening throughout the U.S. Those rates will likely climb.' Any individual person's risk of having an azole-resistant Aspergillus fumigatus is low, Casadevall said. Infections typically affect people who are immunocompromised and amount to around a few thousand cases per year in the U.S., Casadevall said. While relatively uncommon, the bigger risk is the broader trend of drug-resistant fungal infections. 'The organisms that cause disease are getting more resistant to drugs,' he said. 'Even though it's not like Covid, we don't wake up to a fungal pandemic, this is a problem that is worse today than it was five, 10 or 20 years ago.' This article was originally published on
Medscape
04-06-2025
- Health
- Medscape
Fact or Fiction: Ovarian Cancer and Drug Resistance
In ovarian cancer, the emergence of drug resistance has been shown to limit the durability of therapeutic treatment benefit and contribute substantially to ovarian cancer's high mortality rate. Factors such as treatment-free intervals and tumor microevolution may allow for re-sensitization to platinum agents in select patients. In addition to tumor biology, the tumor microenvironment plays a pivotal role in therapeutic resistance. Targeted therapies, once heralded as a solution to chemotherapy resistance, have been shown to face similar obstacles. Drug resistance in ovarian cancer management is an ongoing field of study as clinicians look to limit its impact improve outcomes. Platinum resistance in ovarian cancer is not always permanent. While many patients relapse with tumors less responsive to platinum-based chemotherapy, resistance can be dynamic. Mechanisms such as epigenetic alterations, modulation of DNA damage response, and temporary activation of drug efflux pumps may contribute to reversible resistance. Importantly, a subset of patients initially labeled as platinum-resistant may benefit from platinum rechallenge after a treatment-free interval, particularly if newer maintenance strategies or resensitizing agents are used. This has led to the concept of a "platinum-free interval" to help guide re-treatment. Understanding these nuances is crucial for tailoring treatment strategies and optimizing outcomes. Learn more about medications used in ovarian cancer. While HRD — often due to BRCA1/2 mutations — initially predicts strong sensitivity to DNA-damaging therapies like platinum agents and PARP inhibitors, resistance commonly emerges over time. A key mechanism is the restoration of homologous recombination through secondary or "reversion" mutations in HR pathway genes. These mutations enable tumor cells to resume high-fidelity DNA repair, diminishing the cytotoxic effects of therapy. Additionally, tumors may activate compensatory pathways such as non-homologous end joining or increase drug efflux activity. This resistance may not be detectable at diagnosis and can evolve under therapeutic pressure. Consequently, current research emphasizes longitudinal molecular monitoring to capture evolving resistance mechanisms. Clinically, this underscores the need for re-biopsy or circulating tumor DNA analysis to reassess HR status in recurrent disease, which may influence therapy selection. Learn more about the importance of biopsy in ovarian cancer. Tumor heterogeneity — both genetic and phenotypic — plays a central role in drug resistance and further complications treatment outcomes. Ovarian tumors often consist of diverse subclonal populations, some of which may possess innate resistance traits. Within a single ovarian tumor, multiple subclonal populations may coexist, each with distinct characteristics and sensitivity profiles. When systemic therapy is applied, sensitive clones are eliminated, but resistant ones may persist and expand. Single-cell and spatial transcriptomics studies have mapped how this clonal evolution occurs, revealing that treatment can select for resistant subpopulations not evident at baseline. Heterogeneity also affects the tumor microenvironment and immune response, further complicating therapeutic strategies. Clinically, this variability can manifest as mixed responses, where some lesions regress while others progress. Addressing heterogeneity remains a major challenge and has sparked interest in combination therapies and adaptive trial designs. Personalized treatment strategies based on real-time tumor profiling are likely to improve outcomes by accounting for this complexity. Learn more about ovarian cancer guidelines. Targeted therapies are susceptible to various resistance mechanisms, many of which overlap with those seen in chemotherapy. For example, resistance to PARP inhibitors, widely used in HRD-positive ovarian cancers, can arise from secondary mutations restoring DNA repair function or through enhanced drug efflux. Similarly, resistance to angiogenesis inhibitors may develop via upregulation of alternative pro-angiogenic pathways or changes in tumor vasculature that circumvent the need for VEGF signaling. Resistance is further complicated by factors such as epigenetic reprogramming and altered cell signaling networks. These findings have led to interest in combining targeted agents with immune checkpoint inhibitors, DNA repair modulators, or epigenetic therapies to overcome resistance. Future success with targeted therapy will likely depend on combination approaches informed by tumor genomics and adaptive resistance profiling. Learn more about risk assessment and genetic counseling in ovarian cancer. The tumor microenvironment (TME) is a key contributor to drug resistance in ovarian cancer. Immune cells such as regulatory T cells and tumor-associated macrophages (TAMs) create an immunosuppressive milieu that hinders effective therapy. Additionally, fibroblasts and extracellular matrix components can form physical barriers that limit drug penetration. Cytokines and growth factors secreted within the TME also modulate signaling pathways in tumor cells, promoting survival and resistance. Studies have shown that high TAM density is associated with poor response to both chemotherapy and immunotherapy, and interventions targeting the TME may help reverse resistance. This includes strategies like macrophage reprogramming, TME remodeling agents, and stromal-targeting therapies. Incorporating TME characteristics into clinical decision-making may help guide therapeutic combinations and predict response. Learn more about tumor biomarkers in ovarian cancer.
The Sun
29-05-2025
- General
- The Sun
Warning as deadly fungal infections that enter the bloodstream on the rise – and scientists identify those most at risk
SEVERAL deadly fungal infections are on the rise in England, health chiefs warn - including one labeled a 'huge threat to humanity'. In 2024, cases of fungi entering the bloodstream rose slightly from 3.8 to 3.9 per 100,000 people, new figures from the UK Health Security Agency (UKHSA) reveal. 2 Most were found in vulnerable patients in hospitals, particularly those with weakened immune systems. Bloodstream infections caused by a type of fungus called yeast usually happen in hospitals, from yeasts that naturally live on our skin or inside our bodies. The main culprits behind these new infections are yeast species like Candida albicans, Nakaseomyces glabratus, and Candida parapsilosis. Candida albicans, or C. albicans as it is sometimes called, has already been named by the World Health Organization (WHO) as one of 19 deadly fungi posing a serious threat to humanity. It's branded a superbug because it's becoming harder and harder to treat due to growing drug resistance. But UKHSA chiefs are most concerned about Candidozyma auris - a tougher, drug-resistant fungus that has also been reported and can be deadly and spreads easily in hospitals. Between 2013 and 2024, there were 637 reported cases of in England, with 178 just last year alone, data suggests. Once rare, it's been steadily rising, especially since the Covid pandemic restrictions ended. Experts say the rise may be linked to more complex surgeries, longer hospital stays, and increased antibiotic use – all of which can weaken the body's defenses. 'Our surveillance shows that serious fungal infections are having an increasing impact on public health," Professor Andy Borman from the UKHSA said. "The rise of drug-resistant C. auris means we must remain vigilant to protect patient safety.' To tackle this threat, UKHSA has stepped up surveillance and made C. auris a notifiable infection. This means hospitals must report cases quickly to help control outbreaks. What is antimicrobial resistance? Antimicrobial resistance (AMR) is a global health and development threat. Antimicrobial Resistance (AMR) occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines making infections harder to treat and increasing the risk of disease spread, severe illness and death. As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective and infections become increasingly difficult or impossible to treat. Source: WHO
BBC News
28-05-2025
- Business
- BBC News
The Inquiry Can we stop killer fungi?
Available for over a year Fungal diseases are becoming more common, more dangerous, and more difficult to treat. There's concern that they may cause the next global pandemic. Rising global temperatures, better survival rates for vulnerable patients, and increased medical interventions contribute to the rise in fungal infections. Access to effective diagnostics and treatment remains limited, with significant disparities between high and low-income countries. Treating fungal infections is becoming more challenging as they build resistance to the drugs used to treat them. New therapies are being developed, including treatments that disrupt fungal DNA replication or interfere with essential proteins, offering some hope for long-term control. Contributors: Adilia Warris, Professor in Paediatric Infectious Diseases, University of Exeter, UK Rita Oladele, Professor of Clinical Microbiology, University of Lagos and Lagos University Teaching Hospital, Nigeria Arturo Casadevall, Professor and Chair of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, US Michael Bromley, Professor in Fungal Disease, University of Manchester, UK Presenter: Tanya Beckett Producer: Louise Clarke Researcher: Maeve Schaffer Editor: Tara McDermott Technical Producer: Richard Hannaford Production co-ordinator: Tammy Snow (Image: Aspergillus fumigatus, seen under an optical microscope. Credit: BSIP/Education Images/Universal Images Group via Getty Images)
