Category: 8. Health

In patients with endocrine-sensitive HR-positive/HER2-negative advanced breast cancer, the cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) abemaciclib (Verzenio), palbociclib (Ibrance), and ribociclib (Kisqali) demonstrated varying real-world progression-free survival (rwPFS) outcomes, according to findings from the multicenter PALMARES-2 trial (NCT06805812) published in Annals of Oncology.¹

After a median follow-up of 34.1 months, abemaciclib and ribociclib were associated with significantly longer rwPFS compared with palbociclib. The adjusted hazard ratio (aHR) for abemaciclib versus palbociclib was 0.76 (95% CI, 0.63-0.92; P =.004), whereas ribociclib vs palbociclib showed an aHR of 0.83 (95% CI, 0.73-0.95; P =.007). No significant difference was observed between abemaciclib and ribociclib (aHR, 0.91; 95% CI, 0.73-1.14; P =.425).

In patients with endocrine-sensitive disease, only abemaciclib was associated with better rwPFS when compared with palbociclib (aHR, 0.75; 95% CI, 0.64-0.87; P <.001). In patients who were premenopausal or had endocrine-resistant or luminal B-like disease, abemaciclib and ribociclib were more effective than palbociclib (aHR 0.77; 95% CI, 0.63-0.93, P =.008; ribociclib vs palbociclib: aHR 0.75; 95% CI, 0.58-0.98; P =.034), according to investigators. Abemaciclib was more effective than ribociclib and palbociclib in patients with de novo metastatic disease, and more effective than palbociclib in patients with poorer ECOG performance status. All 3 CDK4/6is were similarly effective in patients who had bone-only disease.

Study Details

A total of 1982 patients were enrolled across 18 Italian cancer centers, in which they received either palbociclib (n = 789), ribociclib (n = 736), or abemaciclib (n = 457), determined by physician choice, in the first-line treatment of HR-positive, HER2-negative advanced breast cancer. Data were collected from electronic health records in each participating center.

Overall, the median age was 63 years (range, 53-72) and of the 1982 patients, 33% had endocrine-resistant tumors, 18% were premenopausal, and 30% had de novo metastatic disease. Abemaciclib-treated patients were more likely to have endocrine-resistant disease, liver metastases and lower progesterone receptor tumor expression, while patients receiving ribociclib were younger and more likely to be premenopausal; finally, palbociclib was more commonly prescribed to patients with a poorer ECOG performance status.

The primary end point was rwPFS, defined as the time interval between the initiation of estrogen therapy (ET) plus CDK4/6is and the detection of disease progression, as evaluated according to radiological (CT/PET scans), clinical (clinical tumor measurements and evolution of patient status), or biochemical criteria (CA15.3 measurements), or patient death, whichever occurred first.

Secondary end points compared the rwPFS associated with the 3 CDK4/6is in clinically relevant patient cohorts, such as premenopausal patients, older patients (age >75 years at the time of CDK4/6i initiation) or patients with liver metastases, bone-only disease, luminal B-like tumors, de novo metastatic disease, or poor ECOG performance status (≥ 1).

Exploratory end points were also explored and included time to next treatment or death, time to chemotherapy or death, and overall survival.

Treatment Discontinuation

Any dose reduction occurred with similar frequency in patients receiving palbociclib (n = 395, 50.9%), ribociclib (n = 349, 48.7%) and abemaciclib (n = 233, 52.4%), and permanent CDK4/6i discontinuation rates for any reason were 484 (61.5%), 290 (39.4%) and 183 (40.0%), respectively. Discontinuation was attributed to disease progression (n = 864, 43.6%), hematological, gastrointestinal and/or liver toxicities (n = 50, 2.5%), or other toxicities/reasons (n = 43, 2.2%).

According to Provenzano et al, “these results…are unique in the field with published works comparing the 3 CDK 4/6is in the real-world setting mostly consist[ing] of relatively small case series lacking sufficient power for effectiveness comparisons…” The investigators also noted a number of limitations with the study, including its retrospective and observational nature and that the prescription of one or another CDK 4/6i may have been influenced by the time of approval and registration of the individual agents.

REFERENCE:

Provenzano L, Dieci MV, Curigliano G, et al. Real-world effectiveness comparison of first-line palbociclib, ribociclib or abemaciclib plus endocrine therapy in advanced HR-positive/HER2-negative BC patients: results from the multicenter PALMARES-2 study. Ann Oncol. 2025;36(7):762-774. doi:10.1016/j.annonc.2025.03.023

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A new study has identified bacterial isolates collected from Crete that are capable of killing mosquito larvae in laboratory tests, raising the possibility of developing biopesticides that target vector species while minimizing environmental impact. The findings, published in Applied and Environmental Microbiology, focus on bacterial strains that produce metabolites lethal to Culex pipiens molestus, a mosquito species known to transmit pathogens such as West Nile virus and Rift Valley fever virus.

Researchers exposed mosquito larvae to extracts derived from the metabolites of bacterial isolates obtained from soil, plants, water and dead insects collected across the island. More than 100 of the isolates tested killed all larvae within 7 days, and 37 did so in under 3 days. Three isolates achieved complete larval mortality within 24 hours. These results suggest that the metabolites produced by the isolates are rapidly acting and may offer a targeted form of mosquito control.

Targeted action with low ecological persistence

The study was conducted as part of the MicroBioPest project, a European Union–funded effort to explore microbial solutions for pest control. Researchers from the Institute of Molecular Biology and Biotechnology (IMBB) in Crete and Johns Hopkins University in Baltimore led the work.

The isolates represented 20 bacterial genera, many of which had not previously been associated with insecticidal activity. Importantly, the study found that the mosquito larvae were killed not through bacterial infection but through exposure to bioactive compounds. This characteristic may allow for the development of products that do not require live microbes to be effective, potentially simplifying formulation and delivery strategies.

Broader applications under investigation

The research team is currently working to identify the molecular composition of the insecticidal compounds. Their analyses aim to determine whether the active agents are proteins or other metabolites. In parallel, the isolates are being tested against other mosquito strains and agricultural pests to assess their broader pesticidal potential.

Biopesticides derived from microbial sources often have low persistence in the environment, breaking down more quickly than synthetic insecticides. While this characteristic reduces ecological accumulation, it may also necessitate repeated application to maintain efficacy. Future work will focus on the development of formulations that enhance stability and usability.

The study underscores the value of biodiversity in identifying new tools for pest management and highlights a potential pathway toward safer alternatives to conventional insecticides.

Reference: Wood MJ, Kanelli K, Silva JJ, et al. Bacteria isolated from biodiverse Mediterranean island habitats yield a large array of biopesticidal metabolites against mosquito larvae. Tortosa P, ed. Appl Environ Microbiol. 2025. doi: 10.1128/aem.00966-25

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Cat’s wild ancestors didn’t get many carbs from their diets of small mammals, reptiles and birds. Before the rise of the pet food industry, domesticated cats likewise only ate the grains and plant sugars that were their prey’s last meals. However, that doesn’t mean cats can’t handle some carbohydrates in their diets. A meta-analysis examining the effects of dietary carbohydrates in commercial cat foods challenged the idea that higher carbohydrate content contributes to obesity, insulin resistance, or elevated glucose levels in cats.

The meta-analysis comprised 16 peer-reviewed studies examining the dietary macronutrient composition and feline metabolic health markers. The outcomes analyzed were body fat mass, fasting insulin and fasting glucose concentrations. The researchers accounted for dietary fat, protein and carb content measured as nitrogen-free extract (% metabolizable energy), as well as daily energy intake and body weight, while also considering individual study design parameters.

Among the 16 studies, the scientists identified three themes.

1. No positive association between dietary carbohydrates and obesity or insulin resistance
Increasing dietary carbohydrate content was not associated with increases in body fat mass, fasted insulin or glucose concentrations. In fact, in lean cats, higher nitrogen-free extract content relative to energy intake was correlated with reduced body fat mass. Fasted insulin levels were more closely associated with body fat and dietary fat rather than carbohydrate content.

2. Dietary fat, not carbohydrate, linked to increases in body fat mass
High-fat diets (>35% metabolizable energy) consistently promoted greater energy intake and weight gain under ad libitum feeding conditions. Several models demonstrated that increased dietary fat, rather than carb content, was a more reliable predictor of higher body fat mass and fasting insulin levels.

3. No significant effect on fasted glucose
Across 14 studies, no significant relationship was observed between macronutrient composition and fasted glucose levels. This may be due to metabolic adaptations of domestic cats. As obligate carnivores, cats prioritize gluconeogenesis from amino acids and show slower glucose clearance rates compared to omnivorous species.

“The results of this meta-analysis indicate that dietary carbohydrates (NFE), included between 2.8% and 57% metabolizable energy, are not a risk factor for greater body fat mass, fasted insulin, and glucose concentrations in cats, suggesting that NFE does not pose a risk for feline obesity, insulin resistance, or hyperglycemia,” the study authors wrote in the Journal of Animal Science. “However, future studies should consider postprandial responses of insulin and glucose to macronutrient compositions to further investigate the role of dietary carbohydrates on insulin resistance in cats, with particular attention to the role of dietary fat, and the role of body condition.”

While the models showed moderate predictive power, limitations included small sample sizes, heterogeneity in study design and lack of control for variables such as sex, age, neuter status and feeding regimen. Most studies fed cats their maintenance energy requirements, potentially minimizing diet-induced changes in body fat mass. Only fasted insulin and glucose values were analyzed to ensure consistency across studies. This limited insight into postprandial metabolic responses, which is potentially a more sensitive indicator of insulin resistance.

Implications for pet food formulation

These findings may prompt re-evaluation of long-held assumptions about the metabolic risks associated with carbs in cat food. While the industry has increasingly shifted toward low-carb, high-protein formulations, the evidence suggests that dietary fat may play a more significant role in driving excess fat storage and insulin issues.

Overall, the analysis highlighted the complexity of pet cats’ metabolism and emphasized the importance of considering both energy intake and body composition in conjunction with macronutrient ratios. As dietary carbohydrate content increases, the displacement of fat or protein must also be considered when assessing metabolic effects.

While carbohydrates have a bad reputation in current human and pet diet trends, evidence suggests that carbs may not always be metabolic villains. Instead, dietary fat intake and overfeeding behaviors warrant closer scrutiny in the fight against cat obesity and metabolic disease. These findings support a more nuanced view of macronutrient formulation in feline diets. Reducing fat levels or monitoring total energy intake may be more effective strategies for managing feline weight and metabolic health than simply minimizing carbohydrates.Tim Wall using DALL-E

CHAMPAIGN, Ill. — Flightpath Biosciences, Inc., a clinical stage biotechnology company focused on the development of precision therapeutics targeting bacterial pathogens, has licensed a class of antibiotics developed at the University of Illinois Urbana-Champaign. The original antibiotic agent, lolamicin, effectively treated bacterial infections in animal models of disease — without wiping out beneficial microbes in the gut. The Illinois team is continuing to develop derivatives of lolamicin.

This class of drugs is notable for sparing healthy microbes but also for targeting pathogenic gram-negative bacteria, the most difficult bacterial infections to treat, said U. of I. chemistry professor Paul Hergenrother, whose lab produced lolamicin and its derivatives.

Hergenrother’s team started its antibiotic-development process by focusing on a suite of compounds originally studied by pharmaceutical company AstraZeneca. These compounds were found to inhibit the Lol system, a lipoprotein-transport system exclusive to gram-negative bacteria.

“Although these progenitor compounds were not effective against bacteria, we recognized that the Lol system was genetically different in pathogenic versus beneficial microbes, making them promising candidates for further exploration,” Hergenrother said.  

In a series of experiments, Hergenrother’s team designed structural variations of the Lol inhibitors and evaluated their potential to kill gram-negative and gram-positive bacteria in cell culture. In the experiments, lolamicin selectively targeted some “laboratory strains of gram-negative pathogens including Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae,” the researchers found. Lolamicin had no detectable effect on gram-positive bacteria in cell culture. At higher doses, lolamicin killed up to 100% of multidrug-resistant E. coli, K. pneumoniae and E. cloacae clinical isolates. 

Further tests demonstrated the drug’s efficacy in animal models of infection. When given orally to mice with drug-resistant septicemia or pneumonia, lolamicin rescued 100% of the mice with septicemia and 70% of the mice with pneumonia, the team reported.

Importantly, detailed analysis showed that lolamicin had no deleterious effect on the gut microbiome of mice, whereas clinically approved antibiotics killed many of these “good” bacteria, disturbing the gut microbiome. These results were published in the journal Nature in 2024.

Pathogenic E. coli and K. pneumoniae are implicated in a host of infections and diseases beyond septicemia and pneumonia, including certain inflammatory conditions and some cancers, Hergenrother said.

“So, we are hoping these new antibiotics can be life-saving drugs for patients with difficult-to-treat infections, but they also could be useful for other indications,” he said.

The lolamicin class of drugs is still early in the drug-development process. Additional preclinical studies must be conducted to demonstrate the lead drug candidate’s safety and efficacy, followed by an “Investigational New Drug” application to the Food and Drug Administration. If all goes well, the company aims to start human clinical trials perhaps as early as 2026, said Matt Tindall, the executive chairman and CEO of Flightpath Biosciences, which has obtained an exclusive global license for all uses of the lolamicin platform.

“The novel mechanism of action and resulting targeted drug candidates are potential game-changers in the treatment of infection-driven diseases, preserving, rather than undermining, an intact healthy microbiome and immune system,” Tindall said. “The lolamicin technology platform is a perfect complement to Flightpath’s strategy of eliminating causal or exacerbating pathogens while sparing the patient’s microbiome.”

“We were attracted to Flightpath as a partner because of its past operational and development successes and its stability as a company,” Hergenrother said. “Flightpath has the capabilities and resources to advance this exciting new technology for patients.”

Hergenrother is a deputy director of the Cancer Center at Illinois and an affiliate of the Carle Illinois College of Medicine and the Carl R. Woese Institute for Genomic Biology at the U. of I.

Editor’s notes:  

To reach Paul Hergenrother, email hergenro@illinois.edu.
To reach Matthew Tindall, email matt@flighpath.bio.   

The paper “A Gram-negative-selective antibiotic spares the gut microbiome” is available online. 
DOI: 0.1038/s41586-024-07502-0

WASHINGTON, D.C. — Thirty-nine percent of respondents to an online poll incorrectly said all processed foods are unhealthy, according to new research by the Physicians Committee for Responsible Medicine published today, July 8, 2025, in JAMA Network Open. When asked which foods increase type 2 diabetes risk, 51% cited sugar, 19% said desserts, and 7% said carbohydrates, in general — all inaccurately.

The Physicians Committee/Morning Consult survey was conducted online among 2,174 U.S. adults Dec. 13 to 15, 2024.

“Foods considered ‘ultra-processed’ can reduce diabetes risk or increase it, depending on which ones they are,” said Neal Barnard, MD, lead author of the paper and president of the Physicians Committee. “Studies show it’s processed meat consumption that is associated with diabetes and cardiovascular disease, not plant-based ultra-processed foods, such as breakfast cereals, which are actually associated with reduced risk of these conditions.”

The news comes on the heels of a new American Medical Association policy supporting public awareness and education about the differences between healthful and unhealthful ultra-processed foods, and just before the federal Food and Drug Administration (FDA) is expected to release a Request for Information for stakeholder input in defining ultra-processed foods.

Though the four-tiered NOVA system developed by Brazilian researchers in 2010 has commonly been used to define ultra-processed foods, the FDA has not formally developed its own definition, which could eventually be used in the next Dietary Guidelines for Americans. The guidelines are used to set the nutritional standards of the National School Lunch Program and other federal food assistance programs.

“It is important that a federal definition of ultra-processed foods reflect scientific evidence and avoids aggravating public confusion,” Dr. Barnard said. “Science shows that ultra-processed foods differ greatly: Certain ones are associated with health problems while others are associated with reduced risk.”

A Harvard University study showed that frequent processed meat consumption was associated with a 44% increased risk of diabetes, while consumption of ultra-processed cereals had the opposite effect—a 22% reduction in diabetes risk.

A recent BMC study showed moderate consumption of muesli and bran cereal correlated with reduced mortality risks related to cardiovascular disease and cancer.

Animal products are a major source of saturated fat in the American diet. A diet high in saturated fat – not carbohydrates — has been shown to reduce insulin sensitivity in as little as four weeks in individuals with a normal insulin sensitivity at baseline, despite no changes in their body weight.

As to the attitudes of U.S. adults, a 2023 survey showed similar results to the recent survey. Respondents’ perceptions of the unhealthfulness of foods correlated strongly with “processing” levels. In the older survey, most young participants failed to identify processed meat as a “processed food.” And while consumption of both processed and unprocessed meat is associated with diabetes (and colorectal cancer and cardiovascular risk), most young participants did not identify these products as increasing the risk of developing type 2 diabetes, even given the rising incidence of diabetes in this group.

“The vague term ‘processed foods,’” Dr. Barnard said, “should be replaced by more specific terms describing foods’ known health effects. Some plant-based foods that are considered processed, such as cereal and canned vegetables and fruit, are actually what Americans need to fight chronic lifestyle diseases like diabetes and cardiovascular disease.”

Note to reporters: To arrange an interview with Dr. Barnard, please contact Kim Kilbride at 202-717-8665 or kkilbride [at] pcrm.org.

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New research has found a novel target with therapeutic potential for metastatic eye melanoma — an aggressive eye cancer — with implications for a range of other cancers.

Published today (4 July) in Nature Genetics, scientists from the Wellcome Sanger Institute and their collaborators used CRISPR screening — a gene-editing tool — to reveal two genes, CDS1 and CDS2, which strongly rely on each other in metastatic eye melanoma. This could pave the way for more targeted and effective cancer treatments, which are currently lacking.

This research advances the scientific understanding of gene targets for a range of cancers but also may provide a hopeful outlook for eye cancer patients with very limited therapeutic options.

Uveal melanoma is a rare but deadly cancer with up to 600 patients diagnosed each year across the UK. There are only four sites across the UK which treat this type of cancer. The treatment options for patients are invasive and include having their eye surgically removed or receiving radiation therapy to the eye. Whilst these treatments are successful and cancer recurrences in the eye rarely happen, approximately half of all patients will go on to develop metastatic disease in the liver within two to three years.

To help address the need for more alternative treatment options, scientists from the Sanger Institute and their collaborators sought to better understand the genetics of uveal melanoma cells.

In a new study, the researchers used a gene-editing tool called CRISPR-Cas9, which enables precise changes to DNA, in order to identify single genes and gene pairs that are essential for the cancer cells to survive and grow. Using CRISPR-Cas9 screening in 10 human uveal melanoma cell lines, the researchers knocked out — or “turned off” — genes individually and in pairs to look for lethal genetic interactions, also known as synthetic lethal pairs.

The researchers identified 76 genes that individually are essential to uveal melanoma and 105 gene pairs that interact lethally when disrupted together.

The key discovery focuses on the genes CDS1 and CDS2, which work together in a way that has not been shown before. Both genes encode enzymes that are involved in phosphoinositide synthesis, which is essential in key cancer pathways including melanoma.

The researchers discovered that cancer cells with low expression of CDS1 are highly dependent on CDS2 for survival. They showed that loss of CDS2 disrupts phosphoinositide synthesis – a type of phospholipid production.6 This leads to impaired tumour growth and cell death — but only when CDS1 expression levels are low. With many normal cells having normal CDS1 expression, this treatment strategy may be able to kill cancer cells, while sparing healthy cells. Reintroducing CDS1 reversed these effects, confirming the dependent role of this gene pair in tumour cell survival.

The researchers then looked at datasets from other types of cancers to reveal that low expression of CDS1 is seen across multiple cancer types. The researchers are now investigating if targeting the CDS1/CDS2 interaction effectively kills cancer cells in these malignancies.

Therefore, the study opens up the idea that the interaction between CDS1 and CDS2 has potential to be a therapeutic target across a range of cancers. The research is a significant stepping stone in providing a hopeful outlook for patients with rare cancers with very few treatment options.

Reference: Chan PY, Alexander D, Mehta I, et al. The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types. Nat Genet. 2025:1-12. doi: 10.1038/s41588-025-02222-1

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The Centers for Disease Control and Prevention is ending its emergency response to bird flu, citing a significant drop in cases between February and July.

The U.S. Department of Health and Human Services announced it is transitioning back to regular program activity, which includes surveillance, readiness and response for influenza, the larger category that includes the H5N1 virus.

The CDC’s avian flu emergency response was declared in April 2024.

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Health experts note that while cases have slowed, bird flu is seasonal, with peaks typically occurring in the fall or early winter, much like the human flu season.

According to the CDC’s website, the public health risk remains low.

RELATED STORY | Hundreds of laid-off CDC employees are being reinstated months after being cut

The latest data states there have been 70 confirmed human cases in the U.S., with one reported death. The CDC said the data will be updated on a monthly basis.

This story was reported on-air by a journalist and has been converted to this platform with the assistance of AI. Our editorial team verifies all reporting on all platforms for fairness and accuracy.