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Pancreatic Cancer Cell Death Triggered by Caspase‑8 Blockade in Preclinical Models

Pancreatic cancer remains one of the most lethal malignancies, notorious for its late detection, rapid progression, and stubborn resistance to many therapeutic strategies clinicians have tried. Despite decades of effort, standard treatments have delivered only incremental gains, and the disease is projected to become the second leading cause of cancer‑related death within this decade. Now, researchers at the University of Cologne’s Center for Molecular Medicine Cologne (CMMC) have uncovered a surprising vulnerability in KRAS‑mutant pancreatic tumors—one that primes them for a potent form of programmed cell death.

In a study published in Nature Communications titled “Oncogenic KRAS-driven type I interferon signaling primes pancreatic cancer for necroptosis,” the team reported that oncogenic KRAS, the defining driver mutation in roughly 90% of pancreatic ductal adenocarcinomas (PDAC), activates a type I interferon signaling program that inadvertently primes tumor cells to necroptosis, an inflammatory form of regulated cell death. However, “KRAS‑mutated tumors have a previously unknown Achilles heel,” said senior author Silvia von Karstedt, PhD. “By switching off the tumor cells’ defense mechanisms, we can significantly kill these tumors.”

The defense mechanism in question is caspase‑8, a protein long known for its role in apoptosis but increasingly recognized as a gatekeeper that prevents necroptosis. The Cologne team found that KRAS‑driven interferon signaling induces high expression of necroptosis‑related interferon‑stimulated genes—including MLKL—creating a state in which tumor cells become heavily dependent on caspase‑8 for survival.

Using genetically engineered mouse models, the researchers showed that deleting caspase‑8 specifically in KRAS‑driven pancreatic lesions triggered widespread necroptotic cell death and eliminated most precursor lesions. “Cancer cell-specific deletion of caspase‑8 is sufficient to trigger necroptotic cell death, eliminating most pancreatic precursor lesions,” the authors reported in their paper.

Furthermore, in aggressive PDAC mouse models and human patient‑derived tumor organoids, pharmacologic caspase inhibition significantly reduced tumor burden.

First author Sofya Tishina, PhD, emphasizes the translational potential: “The findings provide strong evidence that certain forms of pancreatic cancer could be specifically targeted for treatment based on their dependence on caspase‑8. In the long term, this could help develop new therapies for patients who currently have very limited treatment options.”

Beyond pancreatic cancer, the study’s pan‑cancer transcriptomic analysis revealed that tumors with high Ras pathway activity and strong interferon signatures also exhibit elevated necroptosis gene expression, hinting at broader applicability. As the authors concluded in their paper, their work “reveals a KRAS-induced IFN program that sensitizes tumor cells to necroptosis, highlighting a therapeutic vulnerability in PDAC with broader relevance across IFN-activated cancers.”

The post Pancreatic Cancer Cell Death Triggered by Caspase‑8 Blockade in Preclinical Models appeared first on GEN – Genetic Engineering and Biotechnology News.

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Six Takeaways from the Danaher Bioprocessing Summit

The Danaher Bioprocessing Summit, “The Next Era of Bioprocessing: From Promise to Patient Impact,” took place in London earlier this month. The event brought together officials from Danaher companies (Cytiva, Pall, Beckman Coulter Life Sciences, IDBS, and Leica Microsystems), along with biopharma manufacturers and researchers to discuss how the industry can accelerate the transition from scientific breakthroughs to commercial therapies.

Key themes included:

  • AI-driven bioprocess development and manufacturing
  • Intensified and continuous bioprocessing
  • Digitalization and connected data ecosystems
  • Improving productivity and reducing cost of goods
  • Cell and gene therapy manufacturing challenges
  • Scaling production of high-demand biologics, including GLP-1 therapies
  • Advanced analytics and process control
  • Sustainability in biomanufacturing

The conference emphasized that future competitive advantage in biomanufacturing will come less from building additional capacity and more from increasing productivity, speed, and process intelligence across the development-to-manufacturing workflow.

Based on the formal presentations, roundtable discussion groups, and conversations among speakers, panelists, and attendees, six key takeaway ideas emerged.

The old manufacturing playbook no longer fits

Biomanufacturing was built for large batches of standardized therapies. The next generation of medicines—cell and gene therapies, targeted and complex biologics, N-of-1 treatments—doesn’t fit that mold. As molecular diversity increases, the field is shifting toward smaller, parallel and distributed systems that can flex to meet the complexity of individualized medicine. This means faster decision-making, new investment models, and process designs that are data-driven and purpose-built from the start rather than adapted from previous playbooks.

Manufacturing can no longer be treated as a downstream problem. It has to be part of the scientific conversation from day one.

Automation and AI are making personalized scale possible

For years, the promise of personalized medicine ran into a hard wall: you can’t manufacture one patient’s therapy the same way you manufacture a million doses of a traditional drug. Integrating automation, AI and high-throughput experimentation is changing that equation.

These tools are enabling a shift from large-batch production to small-batch and even patient-specific manufacturing while improving efficiency, regulatory consistency, and access to advanced therapies. AI and digital tools are also compressing process development timelines, making it possible to design more tailored, adaptive manufacturing approaches without sacrificing rigor.

Prediction is becoming a competitive advantage

The organizations gaining ground are not merely reacting to problems faster but actually anticipating them. Digital twins powered by integrated data are helping teams model outcomes before committing resources, accelerating timelines and reducing risk. And real-time, molecular and submolecular-level data—shared across interoperable systems—are enabling more precise, proactive decision-making at every stage of development and manufacturing. Investing in this area with critical infrastructure is essential.

Breakthroughs require collaboration across the whole ecosystem

It turned out that the most consistent theme across both days of the Summit was this: no single organization can accomplish what’s needed alone. Partnerships across academia, industry, and regulators are accelerating how all kinds of therapies, especially gene therapies, move from discovery to approved treatment. Earlier alignment between developers, manufacturers, and regulators is reducing friction and compressing timelines.

A central theme surfaced throughout the conference: the science is not the problem. The bioindustry already possesses powerful technologies and therapeutic capabilities. Future success depends on rapidly implementing them through manufacturing, regulatory alignment, supplier collaboration, and partnerships. Organizations that execute most effectively will shape the next decade of medicine. [Danaher]
A central theme surfaced throughout the conference: the science is not the problem. The bioindustry already possesses powerful technologies and therapeutic capabilities. Future success depends on rapidly implementing them through manufacturing, regulatory alignment, supplier collaboration, and partnerships. Organizations that execute most effectively will shape the next decade of medicine. [Danaher]

What makes these partnerships work is not goodwill alone but transparency, shared incentives, and data-driven collaboration that keeps everyone oriented around the same outcomes. The organizations making the most progress are those treating collaboration as a core capability.

 

Regulatory models are evolving with the science, and sustainability is now a procurement requirement, not a values statement 

 

Most of the frameworks that currently govern drug development were built for an earlier era of medicine. As therapies grow more complex and more personalized, those frameworks must change. Early engagement and risk-based approaches are helping bring complex therapies to patients faster without compromising scientific rigor. For rare diseases, which collectively affect an estimated 300 million people worldwide, tailored regulatory pathways are becoming essential.

Summit speakers agreed that regulators are not the obstacle they’re sometimes assumed to be. They want to move faster too, and building the right collaborative infrastructure makes that possible.

Environmental and social criteria are moving from corporate commitments into day-to-day supplier decisions. Organizations are integrating sustainability standards into procurement frameworks, requiring verified supplier commitments and shared performance targets as part of doing business.

Far from being separate from operational strategy, this is part of building supply chains resilient enough to support long-term innovation at scale. Progress toward net-zero goals, Summit participants agreed, accelerates when sustainability is wired into commercial relationships rather than managed alongside them.

Across two days and numerous conversations, one key point kept surfacing: the science is not the problem. The biopharma industry has the tools, the knowledge, and the therapeutic advances to transform how medicine is made and delivered. What it lacks is the collective will to operationalize them at speed. The next phase of progress will be won in manufacturing facilities, regulatory negotiations, supplier contracts, and partnerships that connect all of them.

The final conclusion: organizations that close the gap first will define what the next decade of medicine looks like.

To watch recorded keynote presentations, panel discussions, and fireside chats from the Danaher Summit on Bioprocessing, click here.

The post Six Takeaways from the Danaher Bioprocessing Summit appeared first on GEN – Genetic Engineering and Biotechnology News.

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Digital Technologies for Children With Hearing Impairments to Support Language Learning: Scoping Review

Background: Children with hearing impairments (HIs) have traditionally faced difficulties with language acquisition due to various factors, such as difficulties in accessing early intervention and therapy, among others. There is an opportunity for digital technology to address this problem; however, how different technologies can facilitate language acquisition, as well as the level of evidence, is not well understood. Objective: This study aimed to explore the types, roles, and outcomes of different digital technologies in supporting language development in children with HIs. Methods: Following Arksey and O’Malley’s framework for conducting a scoping review and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews), we systematically searched 6 online databases from 2014 to September 2024 for relevant studies on the role of digital technologies in supporting language learning among children with HIs (aged <18 years). Results: A total of 45 studies met the inclusion criteria. Mobile apps were the most frequently reported technologies, followed by digital books, extended reality, computer-based programs, and tangible or robotic tools. The most commonly used signed-language apps focus on vocabulary development and visual communication. Spoken language tools were less common but included augmentative and alternative communication (AAC) systems and auditory training apps. The efficacy outcomes of 12 studies included in this review showed that AAC-based apps had stronger effects on expressive language, pragmatic communication skills, and vocabulary development. These outcomes occurred when AAC-based apps were used in structured contexts with a therapist or parent. In contrast, signed language apps often reported narrower, word-level outcomes. Notably, relatively few interventions targeted early spoken language development, despite early childhood being a critical period for language acquisition. In addition, limited attention was given to visual design considerations related to user comfort, cultural relevance, and contextual adaptation. Conclusions: The evidence base reveals 3 structural patterns: the dominance of accessibility-driven mobile technologies; an imbalance between signed and spoken-language interventions, characterized by a greater number of signed-language tools but stronger and more consistent evidence for spoken-language outcomes, particularly in AAC-based interventions; and limited integration of digital technologies across home, school, and clinical contexts. Future research should prioritize the co-design and evaluation of culturally responsive, integrated, developmentally appropriate digital systems that support early spoken-language development and sustained, family-mediated language learning across contexts.
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Learning Gain and User Experience of AI Avatar–Based and Human-Presented Explainer Videos: Prospective Randomized Crossover Feasibility Study

<strong>Background:</strong> Explainer videos are widely used in higher education. With the increasing availability of artificial intelligence (AI)–generated avatars, it remains unclear whether the presentation format—human presenter vs AI avatar—affects learning outcomes and user experience, especially in technologically complex fields. <strong>Objective:</strong> This study aimed to assess the feasibility of a randomized crossover design to investigate learning gain and user experience associated with content-identical explainer videos delivered by either an AI-generated avatar or a human presenter. Exploratory analyses examined the potential differences between the presentation formats. <strong>Methods:</strong> An observer-blinded, prospective randomized crossover feasibility study was conducted with 13 undergraduate engineering students. Participants viewed 2 content-identical explainer videos on fuel cell technology presented by either an AI-generated avatar or a human presenter in a randomized sequence. Learning gains were recorded using a 7-item knowledge test administered at baseline and after the first and second video presentations. User experience was assessed after each video by using the AttrakDiff2 questionnaire. Because there was no washout period and the instructional material was identical in both videos, the second learning phase was vulnerable to carryover and test-retest effects. Consequently, analyses of learning outcomes focused on the initial phase, whereas user experience was examined through pooled comparisons across both conditions. <strong>Results:</strong> Both presentation formats were associated with substantial short-term learning gains. The difference in the learning gain between the AI avatar and human presenter videos was not statistically significant (median newly correct items 5, IQR 3-5.5 vs 4.5, IQR 2.5-5; <i>P</i>=.51; <i>Z</i>=0.66; <i>r</i>=0.183). In contrast, user experience ratings were consistently higher for the human-presented video across all AttrakDiff2 dimensions, with small to medium effect sizes. The AI avatar presentation was generally perceived as neutral. <strong>Conclusions:</strong> This study shows that investigating AI-based explainer videos vs those using a human presenter in classroom settings is feasible and highlights methodological challenges, particularly those related to crossover designs involving content-identical materials. In this small exploratory sample, no significant differences in short-term learning gains were detected between different presentation formats. Nonetheless, participants clearly preferred human presenters in terms of user experience. These results should not be seen as proof of equivalence but rather as a foundation for future research with larger sample sizes, improved study designs, and more sensitive outcome measures.
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Feedback-Enhanced Virtual Reality Upper-Limb Training With Body Position Measurement in Healthy Adults: Development and Validation Study

Background: Virtual reality (VR) systems are increasingly used in rehabilitation to facilitate motor learning by providing visual feedback. However, few studies have validated the motion tracking accuracy of VR devices compared with gold-standard motion capture systems. In particular, validation evidence for upper-limb reaching with commercially available VR tracking setups remains limited. Objective: This study aimed to evaluate the validity of a custom VR-based rehabilitation system (VRactice) by comparing its motion tracking data with that of a Vicon motion capture system during a goal-directed reaching task in healthy adults. Methods: This laboratory-based validation study was conducted at Tokyo Kasei University, Sayama Campus, Japan (August-December 2023). Participants were recruited via posted announcements on campus (convenience sampling) and received a 1000 JPY gift card (US $7.00; JPY 142.79=US $1 as of August 1, 2023). A total of 16 healthy participants (n=6, 37.5% male and n=10, 62.5% female participants; mean age 25.3, SD 4.56 years; all right-handed) performed reaching tasks in a VR environment while being tracked simultaneously by both the VRactice system and a Vicon system. Trackers and reflective markers were attached to the hand and elbow to capture 3D coordinates. Each participant performed 10 reaching trials at a frequency of 1 Hz. Data were upsampled to 100 Hz, synchronized, and normalized to the initial position. Valid cycles were identified, and distance time series from the initial position were extracted for the 500-millisecond interval preceding the peak displacement. For each participant, all valid cycles were pooled, and the coefficient of determination () between VRactice and Vicon trajectories was calculated. Of 160 planned trials (16 participants×10 trials), 4 (2.5%) trials were not recorded; the remaining 156 (97.5%) trials were analyzed without imputation. Statistical significance was evaluated at a 2-sided α level of .05. Results: Strong agreement between VRactice and Vicon was observed at both the individual and group levels. The ranged from 0.75 to 0.99 across participants, and all comparisons were statistically significant (<.001). Deviations between the 2 systems remained minimal, confirming that VRactice reliably reproduced the temporal and spatial characteristics of reaching trajectories. At peak displacement, the participant-level mean absolute difference (mean of 10 trials per participant) was 36.5 (SD 29.3) mm (95% CI 20.9‐52.1), suggesting spatial agreement that may be acceptable for upper-limb reaching measurements in this experimental context. Conclusions: The findings support the validity of VRactice in capturing reaching movements with high spatial accuracy compared with a motion capture system. By providing reliable motion data, VRactice may serve as a useful platform for delivering real-time visual feedback and supporting motor training applications in rehabilitation settings. This study is innovative in that it provides formative validity evidence for a VR-based system that integrates real-time trajectory monitoring with adaptive visual guidance, supporting subsequent clinical implementation and evaluation.
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Using In-Home Air Quality Monitoring to Reduce Cannabis Secondhand Smoke Exposure in Children: Quantitative Pilot Feasibility Study

Background: An estimated 5 to 8 million US children live with a parent who uses cannabis, and most cannabis users report smoking cannabis inside their homes, placing children at risk for cannabis secondhand smoke (cSHS) exposure. Indoor air quality (IAQ) monitoring provides real-time feedback on airborne pollutants and has shown promise in reducing in-home tobacco secondhand smoke exposure, suggesting its potential as an effective harm reduction strategy for cSHS. Objective: This pilot study evaluated the feasibility, acceptability, and preliminary effectiveness of using low-cost, off-the-shelf IAQ monitors to increase caregivers’ awareness of children’s cSHS exposure risk and to change smoking behavior. Secondary aims were to assess participant engagement, perceived usefulness, and household communication regarding in-home cannabis smoking. Methods: Between February 2025 and April 2025, 14 adults who smoked cannabis indoors and lived with at least 1 child aged younger than 16 years were recruited primarily via targeted social media advertisements and completed a 3-week trial. Participants received an Awair Element IAQ monitor, printed health education materials, and text messaging prompts for brief surveys. The IAQ monitor continuously measured PM, VOCs, CO₂, temperature, and humidity. Daily surveys captured self-reported PM readings and recent cannabis use, while baseline and end-of-study assessments evaluated IAQ perceptions, cSHS risk awareness, and in-home smoking behavior. Survey results were summarized via descriptive statistics, and linear mixed-effects models were used to characterize objective IAQ trends. Six additional adult household members provided parallel end-of-study data. Results: Reported engagement was high, with 85% (11/13) of participants indicating that they reviewed the monitor at least daily. The average number of days in the previous week that a caregiver reported a child being home while cannabis was smoked declined from 4.5 (SD 2.2) at the trial start to 2.8 (SD 2.9) at the end (6/13, 46% had a reduction; 1/13, 8% reported an increase). Furthermore, 62% (8/13) of participants reported that they reduced (4/13, 31%) or thought about changing (4/13, 31%) their smoking habits. Around 62% (8/13) of participants agreed or strongly agreed that IAQ monitoring helped drive conversations about changing indoor smoking rules, while 100% (13/13) reported no IAQ-driven disagreements among household residents regarding in-home smoking rules. A linear mixed-effects model did not indicate a consistent trend in PM levels across participants over time (β=–0.28; SE 1.13; =.81), but there was heterogeneity in trends, and those with the largest reductions in PM over the trial had the largest reduction in reported children’s cSHS exposure. Conclusions: In-home IAQ monitoring was feasible and perceived as useful among caregivers who smoked cannabis indoors. Real-time IAQ feedback supported risk awareness, promoted family dialogue, and coincided with reductions in in-home smoking around children. These findings suggest that IAQ feedback may represent a scalable tool for reducing children’s cSHS exposure and merits further testing in larger, controlled trials.
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Cancer Diagnostics: Droplet Digital PCR Testing for HPV+ Cancer in the Clinic


Panelists:

Image of Chad Brenner, PhD

Chad Brenner, PhD

Associate Professor of Otolaryngology – Head & Neck Surgery
University of Michigan

Panelist

Image of Chad Brenner, PhD

Chad Brenner, PhD

Chad Brenner, PhD, is an associate professor of otolaryngology – head & neck surgery at the University of Michigan, with joint appointments in pharmacology and membership in the Center for Computational Medicine and Bioinformatics. He directs the Michigan Otolaryngology and Translational Oncology research laboratories, the Translational Innovations Pathology CLIA Laboratory, the Head & Neck Oncology Program and the Cellular and Molecular Biology program. His research focuses on HPV-positive head and neck cancer, circulating tumor DNA diagnostics, HPV integration genomics, and precision oncology approaches to improve cancer detection, monitoring, and treatment response assessment. Brenner’s group developed and clinically implemented MyHPVscore™, a Bio-Rad ddPCR-based assay for detecting circulating tumor HPV DNA in patients with HPV-associated cancers.



Broadcast Date: 

  • Time: 

Human papillomavirus (HPV)-associated cancers, which target the skin and mucus membranes, account for a growing proportion of malignancies worldwide, particularly in the head and neck region. Minimally invasive technologies like circulating tumor DNA (ctDNA) testing are emerging as promising tools for supporting diagnosis, monitoring treatment response, and detecting recurrence. Advances in assay development and PCR platforms are defining how HPV ctDNA tests can be integrated into clinical workflows.

In this IPM webinar, Chad Brenner, PhD, will describe the development, validation, and clinical implementation of MyHPVscore™, a droplet digital PCR-based circulating tumor HPV DNA assay performed on the Bio-Rad QX200 platform. He will highlight the role of HPV ctDNA testing in patients with HPV-positive cancers, including applications for diagnosis support, recurrence surveillance, and clinical monitoring. He will also emphasize the operational experience of establishing and running the assay in a CLIA laboratory, including workflow optimization, assay performance, sample processing, quality control, and integration into clinical and translational research programs. Lastly, his talk will go over ongoing efforts to expand HPV ctDNA testing applications, including future opportunities for broader clinical deployment.

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelist.

Produced with support from:

Bio-Rad logo

The post Cancer Diagnostics: Droplet Digital PCR Testing for HPV+ Cancer in the Clinic appeared first on Inside Precision Medicine.

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Exclusive eBook: How AI is becoming the next military advisor

A collection of stories about how militaries are using AI models to make decisions.

This subscriber-only eBook is a package of six stories that were originally published in MIT Technology Review between April 11, 2025, and April 21, 2026, and have been updated to reflect recent developments.

by James O’Donnell

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