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WASHINGTON — The top contenders to lead the Food and Drug Administration have been sent to the White House for a final review and decision, according to a person familiar with the process.
The finalists include Heidi Overton, a White House adviser; Jeffrey Vacirca, an oncologist and health system executive; and Stephen Ferrara, a health affairs official at the Defense Department.
Cancer cachexia has long been viewed as a systemic inflammatory syndrome driven primarily by tumor-secreted molecules circulating through the bloodstream. Now, a study published in Science suggests that at least one subset of lung cancers may instead exploit the nervous system to trigger appetite loss and rapid weight loss, revealing a potential new avenue for therapeutic intervention.
Using mouse models and supporting clinical observations, researchers found that certain lung tumors produce prostaglandin E2 (PGE2), a lipid signaling molecule that activates sensory neurons in the lung. Those neurons transmit signals through the vagus nerve to appetite-regulating centers in the brainstem, ultimately driving anorexia and cachexia.
The findings challenge the prevailing view that circulating inflammatory cytokines are the primary drivers of cancer-associated wasting and instead point to direct neural communication between tumors and the brain.
“We found that there’s some subsets of lung cancer that are at high risk of developing cachexia,” said senior author Thales Papagiannakopoulos, PhD, from the Salk Institute. “We wanted to understand how the cachexia is actually mediated, and in particular the neurological symptoms related to anorexia—the lack of appetite.”
Cachexia affects up to 80% of patients with advanced cancer and contributes substantially to treatment intolerance, reduced quality of life, and mortality. Despite decades of research, effective therapies remain limited because the biological mechanisms underlying the syndrome have been incompletely understood.
One of the study’s most unexpected findings involved diet.
Clinicians have often recommended calorie-dense, high-fat foods to help patients maintain weight during cancer treatment. Instead, the investigators found that high-fat diets—particularly those rich in animal fats—accelerated cachexia in their lung cancer models.
“We found that high-energy, high-calorie, high-fat diets, particularly animal-containing fat, instead of delaying the weight loss and the cachexia, made it worse,” Papagiannakopoulos said. “That’s quite surprising, but important to know.”
The researchers traced this effect to prostaglandin E2, a bioactive lipid involved in inflammation and known to be regulated by drugs such as aspirin and ibuprofen. Tumors produced higher levels of PGE2 when animals consumed diets rich in animal fat, intensifying appetite loss.
Importantly, the investigators found little evidence that well-known cachexia-associated cytokines, including IL-6 and GDF15, were responsible for the anorexia observed in this model. Instead, the biology appeared to mirror mechanisms previously described during respiratory infections.
Studies of influenza and bacterial lung infections have shown that sensory neurons detect inflammatory signals in the lung and relay information directly to the brainstem, producing sickness behaviors such as reduced appetite, decreased activity, and diminished water intake.
Papagiannakopoulos and colleagues suspected lung tumors were co-opting this same pathway. “The tumors are sort of co-opting these infection-like scenarios,” he said. “They’re signaling to the neurons and, by doing so, directly connecting to the brain and not requiring factors in circulation.”
To test that hypothesis, the researchers disrupted communication between the lung and the brain in two different ways.
In one experiment, they surgically severed one branch of the vagus nerve, reducing neural signaling from the lung by approximately half. The intervention significantly improved anorexia. The team then used chemogenetics—a neuroscience technique that selectively turns specific neurons on or off—to inhibit only lung sensory neurons projecting to the brain. “When we did that, we could rescue the mice,” Papagiannakopoulos said. “They were able to eat and drink and move as if they didn’t have cachexia.”
While surgically interrupting the vagus nerve is unlikely to become a treatment for cancer cachexia, the experiments identified an actionable biological pathway that could be targeted pharmacologically.
One possibility is developing therapies that block the specific prostaglandin receptors on sensory neurons rather than broadly suppressing prostaglandin production with nonsteroidal anti-inflammatory drugs.
“We want to identify what receptors on the neurons prostaglandin E2 is signaling through,” Papagiannakopoulos said. “Then we could potentially use inhibitors against the specific receptors, which would be much more focused than using ibuprofen or aspirin.”
Another approach could involve neuromodulation. Devices that electrically stimulate the vagus nerve are already FDA-approved for certain inflammatory diseases, and early studies are exploring similar technologies in cancer patients.
The researchers ultimately hope to identify the precise population of vagal sensory neurons responsible for transmitting cachexia signals and determine where those neurons communicate within the brain.
Beyond cachexia, the work raises broader questions about how tumors communicate with the nervous system. Rather than acting solely through hormones and inflammatory proteins circulating in blood, cancers may directly manipulate neural circuits to produce many of the systemic symptoms experienced by patients.
“The brain acts as a central integrator of all these signals coming from the body,” Papagiannakopoulos said. “We actually think that a lot of the effects seen in cancer patients—some of them grouped under cachexia or other paraneoplastic syndromes—are mediated through the brain through these neural networks.”
If confirmed in patients, those neural pathways could represent an entirely new class of precision medicine targets aimed not at shrinking tumors themselves, but at preventing one of cancer’s most devastating complications.
The post Lung Tumors Hijack Nerve Signals to Drive Cachexia, Opening New Therapeutic Target appeared first on Inside Precision Medicine.
BOSTON — Governor Maura Healey has summoned the state’s largest health system and its striking nurses to the State House on Wednesday in an attempt to broker a new contract, according to the Massachusetts Nurses Association.
The calling of the late-afternoon meeting came hours after a boisterous start to Massachusetts’ biggest-ever nurses strike, and the first at Brigham and Women’s Hospital. Mayor Michelle Wu also helped arrange the meeting, the union said.
Thousands of Brigham nurses and supporters poured onto Francis Street near the hospital starting at 7 a.m., shaking cowbells, banging on plastic buckets and cheering at a deafening chorus of supportive honks from passing cars. The nurses, sporting “Union Strong” and “Brigham Nurses United” shirts, waved signs calling out management. “Value Nurses Like You Value Your Bonu$e$,” one sign read.
Fast, local cryopreservation is a consistent bottleneck for autologous cell therapy developers, even in major cell and gene therapy hubs. For the peripheral blood mononuclear cells (PBMCs) that form the foundation of immunotherapies, vaccine development and autologous therapies, every hour between leukapheresis collection and cryopreservation can degrade cell viability and functional integrity.
OrganaBio’s new PBMC isolation facility in San Diego removes that bottleneck for one of the three major cell and gene therapy hubs in the world. The opening of the new PBMC processing and cryopreservation laboratory at Excellos Labs (which OrganaBio acquired in May) makes it possible to isolate and cryopreserve PBMCs within three to four hours of collection, rather than losing time and quality by shipping live material across the country.
“The quality you lock in at cryopreservation is the quality the developer gets back months later,” Justin Irizarry, CEO, OrganaBio, tells GEN. “Get the first few hours right and you have protected everything downstream. Having that processing happen locally is what makes the few-hour window realistic rather than aspirational.”
The San Diego lab reports an average PBMC viability of “around 99.1% and recovery above 2.9 million cells per milliliter, with consistency from batch to batch,” Irizarry says. He credits those statistics to rapid time to cryopreservation, validated standard operating procedures “including sponsor-specific protocols,” personnel trained in each of those procedures, and a single quality system for each of OrganaBio’s sites. That combination ensures consistency across batches and sites, so “a sample processed in San Diego is indistinguishable from one processed in Miami,” he emphasizes.
In contrast, one German study comparing cells cryopreserved within six hours or 20 hours of collection notes a higher percentage of apoptotic natural killer (NK) cells associated with the longer hold time. Specifically, after 20 hours, 41% of the cells were apoptotic versus 24% for those preserved within six hours of collection. Robustness also declined with the longer hold times.
Robust local sourcing for PBMCs is a strategic advantage for San Diego’s clinical-stage biotherapeutic developers. In addition to gaining higher-quality starting materials, they can expect to benefit from tighter manufacturing timelines and less supply chain risk. Local processing reduces the inherent risk associated with cold-chain and transportation variables, while enhancing redundancy provided by OrganaBio’s West Coast sites in San Diego, Irvine, and San Francisco Bay, and its East Coast headquarters in Miami.
OrganaBio expects continued growth, “including clinical trial services, manufacturing services, and product manufacturing,” Irizarry says. The company is onboarding new customers and programs and deepening relationships with existing customers. “We also will evaluate opportunities to expand into additional markets for clinical trial services, particularly where there is strong population growth, good ethnic and racial diversity, and a lack of professionalized PBMC isolation services in the market.”
The post Local PBMC Isolation Enables Four-Hour Processing in San Diego appeared first on GEN – Genetic Engineering and Biotechnology News.
Achieving end-to-end continuous bioprocessing without introducing surges and pooling remains a goal for biomanufacturers. As they transition from vat to hybrid or continuous processing, biomanufacturers optimize individual steps but often overlook their interfaces, creating an imbalance in the system.
“The primary barrier to end-to-end continuous biomanufacturing is often not the lack of continuous unit operations themselves. The larger challenge is integrating technologies such as perfusion culture, multicolumn chromatography, continuous viral inactivation, and continuous filtration into a coordinated manufacturing train,” Moo Sun Hong, PhD, assistant professor, Seoul National University, tells GEN.
“Our review suggests that unresolved interface mismatches between unit operations, particularly between steady upstream harvest and cyclic downstream purification, remain the dominant obstacle to achieving true end-to-end continuity,” Hong says. Interface engineering is vital to manage throughput, residence times, process robustness, and product quality across interconnected units.
One part of the study compared batch and continuous biopharmaceutical manufacturing across 10 metrics, while another considered the various degrees of continuous processing. They concluded that the advantages of continuous processing result mainly from process intensification, which, in itself, introduces new vulnerabilities such as measurement latency and uncertainty around residence time distribution.
The challenge for manufacturers is that limited coordination between upstream and downstream processing results in flow-rate mismatches. “Unit operations operate with fundamentally different dynamics,” Hong acknowledges. “Upstream perfusion generates a relatively steady harvest stream, whereas many downstream operations operate cyclically. This creates flow-rate and residence-time mismatches that often require surge tanks or hold steps. Eliminating these interruptions requires careful interface engineering, synchronization of cycle times, real-time monitoring, and coordinated control across the entire process train.”
Hong and colleagues recommend evaluating batch-to-continuous processing transitions based upon “integrated techno-economic, sustainability, and operational performance metrics rather than isolated unit-operation productivity alone.” Therefore, process engineers can design the interfaces and control strategies in a way that enables a fully-connected, automated, continuous manufacturing platform that functions in a near steady-state without the need for holding tanks between units.
In a continuous processing environment, control strategies based on process analytical technology (PAT) and digital twin technology are vital. Hong calls them “the backbone of integrated continuous manufacturing.”
Specifically, PAT provides visibility and real-time monitoring for rapid responses to process variances, while digital twins provide enhanced predictive models, as well as fault detection, optimization, and analysis. Additional automation and control architectures also should be included “…that connect sensors and programmable logic controller/supervisory control and data acquisition (PLC/SCADA) systems, as well as process data repositories, control loops, and supervisory models across the integrated process train,” the scientists advise.
“In our view,” Hong concludes, “the challenge is not simply making individual operations continuous, but making the entire manufacturing platform function as an integrated system.”
The post Interface Mismatches Remain Key Barrier to Continuous Bioprocessing appeared first on GEN – Genetic Engineering and Biotechnology News.
Background: Acute kidney injury (AKI) is a frequent and serious complication among hospitalized patients, particularly in critical care settings, where its incidence can exceed 50%. AKI is associated with increased mortality, prolonged hospitalization, dialysis dependence, and higher health care costs. Although the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines emphasize supportive care, hemodynamic optimization, and avoidance of nephrotoxins, their implementation remains inconsistent, partly due to the lack of timely risk stratification. Recent advances in artificial intelligence have enhanced early prediction and detection of AKI, offering new opportunities to improve patient outcomes and intensive care unit (ICU) efficiency. The U-Care Renal Platform (UCRP; U-Care Medical S.r.l), a Conformité Européenne (CE)–marked artificial intelligence–powered medical device, integrates directly with the ICU electronic health record to continuously analyze patient data and predict the risk of moderate or severe AKI within 24 hours, providing actionable, guideline-based recommendations. While the predictive performance of UCRP has been validated previously, its real-world impact on clinical and operational outcomes in the ICU remains underexplored. Objective: This single-center uncontrolled before-and-after implementation study aims to evaluate the association between UCRP implementation and selected ICU clinical and operational outcomes in routine practice at SCIAS Hospital, Barcelona. Methods: This study was conducted as a retrospective service evaluation of a workflow-embedded clinical decision support system between March 2023 and March 2025. It included 202 postsurgical adult ICU patients. Outcomes of interest were assessed by comparing preimplementation and postimplementation periods. Months during which the UCRP was inactive were excluded from the analysis (total excluded duration: 10 months; 5 in the preimplementation period and 5 in the postimplementation period). The outcomes included the incidence of moderate-to-severe AKI (KDIGO stages 2 and 3), the use of nephrotoxic medications, the frequency of hypotensive episodes among patients with AKI, and the ICU length of stay. Results: During the postimplementation period, lower rates of moderate-to-severe AKI (9/99, 9.1% vs 12/103, 11.7%), nephrotoxic drug administration, and hypotensive episodes among patients with AKI were observed compared with the preimplementation period. Conclusions: Integration of the UCRP into ICU workflows was associated with differences in selected AKI-related process and intermediate clinical outcomes in this single-center uncontrolled before-and-after implementation study. However, given the study design, causal relationships cannot be established, and the findings should be interpreted as preliminary signals requiring confirmation in larger, controlled, and multicenter studies, including patient-centered outcomes.
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WASHINGTON — Last week, pharmaceutical leaders filed into a meeting room in the Eisenhower Executive Office Building, next to the White House, for a meeting with Secretary of State Marco Rubio, health secretary Robert F. Kennedy Jr., and HHS Chief Counsel Chris Klomp.
The administration officials had a message for the industry: It’s time to bring production of essential medications back to the U.S. — or at least closer to home.
The meeting, described by an administration official and two people familiar with the event, focused on increasing U.S. control of the supply chains for the 86 medicines deemed essential by the health department’s Assistant Secretary for Preparedness and Response.
A study carried out in Estonia on healthy relatives of breast and ovarian cancer patients shows around 20% of those tested carried some form of genetic variant that increased their risk of developing cancer.
The study showed that BRCA1/2 cancer-associated variants, currently the most widely recognized and tested cancer predisposition genes overall, accounted for 58.4% of all pathogenic variants uncovered by the investigators, but 41.6% were in non-BRCA genes.
“A carrier rate of 19.7% is remarkably high compared with the general population and strongly supports broader and more systematic genetic testing of relatives in families affected by breast and ovarian cancer,” lead investigator Mikk Tooming, PhD, a researcher at the Institute of Clinical Medicine in Tartu, Estonia, told Inside Precision Medicine.
“The highest yield was observed when a pathogenic variant was already known in the family… However, even among relatives without a previously identified familial variant, 8% carried a pathogenic variant. This is a clinically meaningful detection rate and suggests that genetic testing should not be restricted only to families in which a specific variant has already been identified.”
The current study, published in Frontiers in Genetics, included 3,472 healthy family members of people with breast and ovarian cancer. Of these individuals, 88% were female and 12% male. Most of those tested (79%) were younger than 51 years, which is when cancer screening often starts.
The researchers retrospectively analyzed genetic results from the family members, tested at four hospitals between 2007 and 2023. Testing evolved from targeted Sanger sequencing and microarrays in the early years to broad multigene next generation screening panels covering up to 6,700 genes by 2023.
Overall, around 20% of the tested family members carried a pathogenic or likely pathogenic variant. This went up to 41.8% when a familial variant was already known, versus 8.0% when it was not. BRCA1/2 variants accounted for most variants, but 23 genes were implicated in total, with CHEK2, ATM, BRIP1, and PALB2 also prominent.
Notably, the youngest group tested, those who were 30 years or younger, were more likely to have a cancer risk variant than older groups with a rate of 28%. “Age is highly relevant because many hereditary cancer syndromes begin to confer increased cancer risk well before routine screening starts,” says Tooming. “Identifying carriers early allows surveillance and prevention plans to be implemented at the most appropriate time.”
Despite being under tested, the carrier rate of risk variants in the men tested was high at 34%. Breast and ovarian cancers are thought of as predominantly female conditions. While women may be more impacted by these cancers than men, men can also carry relevant risk variants and these can increase their risk of developing other cancers.
“Both healthcare providers and families may focus testing efforts on women, unintentionally overlooking men,” emphasizes Tooming. “This highlights a significant gap in current practice. Male carriers, particularly those with BRCA2 variants, have elevated risks of prostate cancer, male breast cancer, pancreatic cancer, and several other malignancies. Health systems should actively promote genetic counselling and testing for male relatives when hereditary cancer risk is suspected.”
The researchers support expanded testing but believe that earlier and more personalized genetic risk assessment, for example, in families known to be impacted by cancer, would produce better results than simply lowering the age of cancer screening.
“The data suggest that individuals from families affected by breast and ovarian cancer should undergo earlier evaluation for hereditary cancer risk. When a pathogenic variant is identified, surveillance should be tailored according to the specific gene and associated cancer risk,” says Tooming.
“While our study did not include longitudinal follow-up and therefore cannot directly measure reductions in cancer incidence or mortality, the high proportion of carriers identified before standard screening age strongly suggests that expanded testing has the potential to deliver substantial public health benefits in Estonia and elsewhere.”
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