Tag: Academic research

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Proteins.1 Launches to Develop Single Molecule Protein Amplification Tech for Diagnostics

Finnish deep-tech startup, Proteins.1, launched with €4.7 million in pre-seed funding, led by Lifeline Ventures and Cloudberry Ventures, with in-kind support from VTT and Business Finland. Harnessing technology transferred from VTT Technical Research Centre of Finland, Proteins.1 is developing a PCR-like enzyme-free, ultra-sensitive amplification platform for the detection of proteins at the single-molecule level. The firm says it aims to transform early disease diagnostics by enabling detection of disease-related molecular warning signals long before there are clinical signs.

While polymerase chain reaction (PCR) technology has transformed modern diagnostics by allowing tiny amounts of DNA to be amplified into detectable signals, no equivalent amplification method has existed for proteins, which often signal the earliest onset of cancer, neurodegeneration, cardiovascular disease, and inflammatory conditions, the company notes. Proteins.1 aims to leverage its technology to establish a new category of ultra-sensitive protein diagnostics, combining high multiplexing, scalable chip-based detection, and significantly lower capital costs compared to existing systems.

The patented, physics-based technology introduces cyclic signal amplification for proteins, potentially enabling up to 1,000 times better sensitivity than current gold-standard platforms, Proteins.1 claims. Unlike conventional immunoassays that rely on enzymatic reactions prone to variability and noise, the Proteins.1 approach is solid-state, enzyme-free, and compatible with semiconductor-based photonic detection.

The platform replaces enzymatic signal amplification with a physics-based magnetic cycling mechanism that repeatedly reads a single captured protein molecule, accumulating signal clarity without increasing background noise. The company says this supports ultra-high sensitivity combined with high multiplexing, potentially enabling the simultaneous measurement of hundreds of biomarkers from a few drops of blood.

“For decades, diagnostics has been limited not by biology, but by what our instruments can detect,” commented Proteins.1 co-founder and CEO Prateek Singh, who is inventor of the core technology. “The body produces early warning signals long before disease becomes visible. Our mission is to make those signals measurable and actionable, years earlier than today.”

Built on research conducted at VTT and further validated through European Union breakthrough innovation funding, the technology has been granted U.S. and Finnish patents, and additional international applications are pending. Initially, the company aims to develop research-use-only applications in oncology, neurology, and immunology, before progressing toward regulated clinical diagnostics. “Early detection dramatically improves survival rates in diseases such as cancer and neurodegenerative disorders,” Singh continued. “If we can detect disease at the molecular stage rather than the symptomatic stage, we entirely change treatment possibilities.”

Proteins.1 plans to expand its engineering and product development team in Finland during 2026–2027, positioning itself as a European hub for next-generation diagnostic technology. “Proteins.1 represents the kind of deep scientific breakthrough that can redefine an entire industry,” said Jyri Engeström at Lifeline Ventures. “The team combines world-class research with proven experience in building and scaling regulated medtech businesses.” Cloudberry Ventures further highlighted the company’s strong alignment with European strengths in photonics, microfabrication, and precision engineering.

Added Rene Kromhof, at Cloudberry VC, “What sets Proteins.1 apart is a fundamentally new sensing approach. Rather than using enzymes that give you one chance to detect a protein, they use light and thin-film transistors to amplify the signal from a single protein until it rises above the noise. That dramatically improves sensitivity, and ultimately, how early disease can be caught.”

CEO Prateek Singh has previously raised venture capital for microfluidics ventures and holds multiple patent families. Co-founder and COO Harri Hallila previously built and exited a regulated medical device company. The broader team includes commercial leadership with experience in leading diagnostics platforms.

The post Proteins.1 Launches to Develop Single Molecule Protein Amplification Tech for Diagnostics appeared first on GEN – Genetic Engineering and Biotechnology News.

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Advances in Stem Cell‑Derived Insulin‑Producing Cells for Type 1 Diabetes

Researchers at Karolinska Institutet and KTH Royal Institute of Technology have developed an improved method for creating insulin-producing cells from human stem cells. In a newly published study, the team demonstrated that these cells effectively regulate blood sugar levels in laboratory tests and can reverse diabetes in mice.

“We have developed a method that reliably produces high-quality insulin-producing cells from multiple human stem cell lines,” said Per-Olof Berggren, PhD, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “This opens up opportunities for future patient-specific cell therapies, which could reduce immune rejection.” Berggren and Siqin Wu, PhD, researcher at Spiber Technologies AB (formerly at Karolinska Institutet), are co-corresponding authors of the researchers’ published paper in Stem Cell Reports, titled “An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines.”

Type 1 diabetes (T1D) occurs when the immune system destroys insulin-producing cells in the pancreas, meaning the body can no longer absorb glucose from the blood and regulate blood sugar levels. “In type 1 diabetes (T1D), autoimmune destruction of β cells results in loss of glycemic control,” the authors wrote.

One possible treatment strategy is to replace these cells with new ones. However, previous methods of producing such cells from stem cells have often yielded mixed results. Stem cell therapy for type 1 diabetes is already being tested in several clinical trials. However, a challenge with previous methods is that the stem cells often develop into a combination of the desired and undesired cell types, increasing the risk of complications. Another challenge is that the insulin-producing cells created are often not mature enough to respond well to glucose.

“The success of cell therapy for type 1 diabetes (T1D) depends on reliable differentiation of stem cells into functional pancreatic islets,” the authors noted. They pointed out that previous protocols have exhibited variable efficiency across different human pluripotent stem cell (hPSC) lines. “Differentiation beyond the stage (S) 4 pancreatic progenitor (PP) stage frequently yields heterogeneous cultures containing proliferative non-endocrine cells and immature endocrine cells … increasing the risk of cyst or tumor formation,” the team further commented.

The newly optimized production process reported by Berggren and colleagues yields more mature and purer insulin-producing cells than previous methods. In a laboratory setting, the cells were able to secrete insulin and responded strongly to glucose. When the researchers transplanted these cells into streptozotocin (STZ)-induced diabetic mice, the animals gradually regained the ability to regulate their blood sugar. “By adjusting the culture steps and allowing the cells to form three-dimensional clusters themselves, many unwanted cell types are eliminated and the cells gain a better ability to respond to glucose, according to the researchers. “Single-cell analyses show that the SC-islets are free of non-endocrine cell populations before and after transplantation,” the team stated.

The transplantation was performed in the anterior chamber of the eye (ACE) which provides a transparent and accessible site for noninvasive monitoring of engrafted SC-islets through the cornea, the team pointed out. Transplantation into this compartment is also straightforward and minimally invasive.  In their paper, the team noted, “Intraperitoneal glucose tolerance tests (IPGTT) at three, four, and six months post-transplantation showed improved glucose handling over time … SC-islet transplantation reversed hyperglycemia by three months, and by five–six months blood glucose levels fell slightly below pre-STZ baselines.”

Berggren commented, “This is a technique we use to monitor the development and function of the cells over time in a minimally invasive way. We observed that the cells gradually matured after transplantation, retaining their ability to regulate blood sugar for several months, which demonstrates their potential for future treatments.”

Fredrik Lanner, PhD, professor at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and last author of the paper, added, “This could solve several of the problems that have previously hindered the development of stem cell-based treatments for type 1 diabetes. Building on this, we will work towards clinical translation aiming at treating type 1 diabetes.” In their report the authors concluded, “Our protocol generated glucose-responsive SC-islets from all eight hPSC lines tested … demonstrating potential for autologous applications … Our efficient differentiation protocol represents a key step toward autologous cell therapy, though further work is required to realize this goal.”

The post Advances in Stem Cell‑Derived Insulin‑Producing Cells for Type 1 Diabetes appeared first on GEN – Genetic Engineering and Biotechnology News.

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Aging Immune Cells Linked to Fatty Liver Disease 

UCLA researchers have found that macrophages with a senescent phenotype may be actively driving progression of fatty liver disease. A study published today in Nature Aging reports that clearing this aging cell population in mice dramatically reduced liver inflammation and reversed damage even without any dietary changes. 

“Senescent cells are fairly rare, but think of them like a broken-down car,” said Anthony J. Covarrubias, PhD, assistant professor at the UCLA David Geffen School of Medicine and senior author of the study. “Just one stalled car can back up traffic for miles. Now imagine five or ten of them slowly accumulating. That’s what these cells do to a tissue: even a small number causes enormous disruption.”

As cells age and become senescent, they are known to drive chronic inflammation across a range of tissues. While previous research has shown that eliminating senescent cells can improve health and lengthen lifespan, there is still a limited understanding of which cells undergo the senescence process and how to distinguish them from healthy cells.

This is especially the case for cells that naturally share hallmark features with senescent cells, as is the case of macrophages; when activated, macrophages secrete a range of inflammatory cytokines and immunomodulatory metabolites that many senescent cells also produce when driving chronic, age-driven inflammation. 

The researchers found that no single biomarker was enough to identify senescent macrophages. Instead, they identified that this aging cell population was defined by the simultaneous expression of p21 and Trem2 proteins, together with altered nuclear morphology, lipid metabolism and type I interferon (IFN) hyperactivation.

In mice, senescent macrophages carrying this molecular signature were found to surge from 5% in young mice to up to 80% in older ones, correlating with a rise in chronic liver inflammation during normal aging. In addition, excess cholesterol was found to push macrophages into a senescent state where they stopped dividing, increased secretion of inflammatory proteins and activated expression of p21 and Trem2. 

“Physiologically, macrophages can handle cholesterol metabolism,” said Ivan A. Salladay-Perez, graduate student in the Covarrubias lab and lead author of the study. “But in a chronic state, it’s pathological. When you look at fatty liver disease, which is driven by overnutrition and too much cholesterol in the blood, that excess cholesterol appears to be a major driver of the senescent macrophage population.”

Experiments using a publicly available genomic dataset of patient liver biopsies found that the same senescent macrophage signature was increased in diseased livers compared to healthy ones, suggesting they also play a role in chronic liver disease in humans. 

In mice with a high-fat, high-cholesterol diet, a drug that selectively kills senescent cells was found to reduce overall body weight and make livers healthier—smaller and with a lower fat percentage. These findings suggest that clearing senescent macrophages from the liver does not just slow the progression of fatty liver disease, but can actually reverse it without changing the diet. 

Because the drug tested in mice is too toxic for humans, the researchers plan to begin drug screening studies to identify new compounds that can replicate these effects. They will also be exploring whether this therapeutic target could be expanded to a range of other age- and cholesterol-driven conditions where senescent macrophages have been observed.

“It all goes back to understanding how these cells arise in the first place,” said Salladay-Perez. “If you really understand the basic mechanisms driving inflammation with aging, you can target those same mechanisms to treat not just fatty liver disease, but atherosclerosis, Alzheimer’s and cancer.” 

The post Aging Immune Cells Linked to Fatty Liver Disease  appeared first on Inside Precision Medicine.

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Neurodegeneration in ALS and FTD May Be Caused by Somatic “Mosaic” Mutations

Scientists at Boston Children’s Hospital and Harvard Medical School have uncovered evidence that rare, localized genetic mutations may spark the onset of devastating brain diseases even when those mutations are present in only a tiny fraction of cells.

The Nature Genetics study, which focused on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), discovered that these conditions can start with somatic “mosaic” mutations that spread throughout the nervous system.

Despite the association of a handful of genes with these neurodegenerative diseases, 90–95% of cases arise sporadically, without a family history, leaving their origins unclear. Researchers genomically examined 1,787 postmortem tissue samples of various brain regions and spinal cords from hundreds of patients (144 control, 291 ALS, and 117 FTD) who died before the age of 45 but had no family history. The samples were taken from the NIH NeuroBioBank.

Using molecular inversion probe (MIP)-panel sequencing of 88 neurodegeneration-associated genes, they discovered that about 2.1% of sporadic cases carried damaging somatic mutations in one of these disease-related genes. These mutations were extremely rare within the tissue, often present in less than 2% of cells. What makes the discovery noteworthy is where those mutations appear: rather than being distributed throughout the brain, they were concentrated in disease-affected areas, such as the motor cortex and spinal cord in ALS. This pattern suggests that neurodegeneration may begin in a small cluster of genetically altered cells before spreading outward. That idea aligns with existing theories that ALS and FTD progression involve the movement of toxic proteins, particularly TDP-43, between cells in a prion-like manner. A single focal mutation could initiate this cascade, effectively “seeding” disease.

Senior author Christopher A. Walsh, MD, PhD, Howard Hughes Medical Institute investigator and professor at BCH and HMS, told Inside Precision Medicine, “Above all, it suggests that the genes, or at least some of the genes, that drive the disease don’t necessarily have their toxic effects only in the neurons carrying the mutation. Or that some neurons are impacted and that leads to a domino effect that somehow impacts neurons that don’t carry the mutation.”

The study also identified mutations in unexpected genes, including DYNC1H1 and LMNA, which are typically linked to severe childhood neurological disorders. Inherited versions of these mutations are often incompatible with long-term survival, but when present only in a subset of brain cells, they may allow normal early development followed by late-onset neurodegeneration. In another key finding, researchers detected spontaneous expansions in the C9orf72 gene—the most common genetic cause of inherited ALS and FTD—arising directly within brain tissue. This provides some of the first evidence that such disease-causing expansions can occur somatically rather than being inherited.

Together, the results point to a new model of disease: ALS and FTD may not always begin with widespread genetic risk but instead with rare, localized mutations that trigger broader neurodegeneration over time. The discovery also highlights a major challenge for diagnosis. Because these mutations can be confined to the brain and present at extremely low levels, they would likely be missed by standard genetic tests using blood or saliva.

According to Walsh, the results highlight the importance of creating a more sophisticated clinical strategy. “Clinically translating these findings immediately is a challenge, because most of the variants we find are likely limited to the brain and hence unavailable to clinical sequencing,” said Walsh.

The researchers believe that these findings pave the way for novel methods, both for identifying concealed genetic alterations in the brain and for creating treatments that target early, localized disease processes before they proliferate.

Walsh said, “If we see that gene-directed anti-sense oligonucleotide (ASO) therapies (like the ongoing FUS trial) are incompletely effective, it could reflect that the degeneration is a widespread process. Or it may suggest the importance of starting these ASO trials at the earliest possible stage to try to block secondary processes.”

While the proportion of cases explained by these mutations is still small, the work underscores a growing realization in neuroscience: even a handful of altered cells may be enough to set off widespread brain disease.

The post Neurodegeneration in ALS and FTD May Be Caused by Somatic “Mosaic” Mutations appeared first on Inside Precision Medicine.

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Artificial Intelligence Design for Race-Based Prostate Cancer Stage Classification With Multilayer Perceptron: Feature Selection Optimization Approach

Background: Prostate cancer progression exhibits significant variability influenced by biological and racial factors. DNA methylation profiling has shown potential in early cancer detection, but its integration with machine learning across racially diverse populations remains limited. Objective: This study aimed to develop a prostate cancer stage classifier for the majority White cohort using DNA methylation data and a multilayer perceptron (MLP) model in order to classify prostate cancer stages into early (stages I-II) and late (stages III-IV) stages and assess its performance when applied to other racial groups to highlight the need for race-specific models. Methods: Methylation and phenotype data from the TCGA-PRAD (The Cancer Genome Atlas Prostate Adenocarcinoma) dataset were processed using differentially methylated position (DMP) analysis to identify CpG sites correlated with cancer stages. These features were further refined through recursive feature elimination (RFE) and used to train MLP models. Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) were used to interpret the model and identify key DNA methylation features contributing to model predictions. Results: The best-performing model achieved 95% accuracy and up to 99% area under the curve on the majority race (White) training data using 90 selected features. However, performance declined sharply in racial minority groups, revealing the effects of sample imbalance and race-specific methylation patterns. Feature importance examination indicated strong patterns within certain CpG sites driving model predictions. Conclusions: We propose a race-aware MLP model for prostate cancer stage classification using DNA methylation data, which has been optimized through DMP and RFE-based feature selection. SHAP and LIME confirmed the predictive relevance of selected CpG sites, supporting model transparency. The results highlight high performance within the White cohort but reveal poor generalization to racial minority groups, emphasizing the importance of race-specific modeling strategies.
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A Digital Inclusion Intervention to Improve Access to a Digital Health Intervention Among Digitally Excluded Adults: Mixed Methods Pilot Randomized Controlled Trial

Background: The National Health Service 10-year health plan emphasizes an increasing shift toward digital health care delivery. However, there is limited research on how best to support, engage, and include individuals who are digitally excluded. As health care services become more digitally driven, evidence-based interventions are needed to address digital exclusion and ensure equitable access to care, particularly for people living with long-term conditions. Objective: This study aimed to evaluate the feasibility and acceptability of providing digital literacy training alongside a digital health intervention (DHI; Ex-Tab intervention), compared with providing a DHI alone. Kidney Beam, a DHI designed to promote physical activity and improve quality of life in people with chronic kidney disease (CKD), was used as an exemplar DHI. Methods: This mixed methods, single-site pilot randomized controlled trial recruited 40 adults with CKD who were digitally excluded. Digital exclusion was defined as lacking access to a Wi-Fi–enabled digital device or having a Digital Health Care Literacy Scale (DHLS) score of <7 (range 0‐21). Participants were randomized 1:1 to receive either the Kidney Beam Ex-Tab intervention or Kidney Beam alone (control). The intervention group received a Wi-Fi–enabled iPad on loan with Kidney Beam preinstalled, digital literacy training, and ongoing support to access the 12-week Kidney Beam program (twice weekly live exercise and education sessions). The control group received sign-up instructions for Kidney Beam only. Feasibility outcomes were assessed against a priori progression criteria and included screening, recruitment, retention, adherence, safety, and acceptability. Secondary outcomes included the Kidney Disease Quality of Life Questionnaire, Chalder Fatigue Questionnaire, and Patient Health Questionnaire-4. Outcomes were measured at baseline and 12 weeks. Acceptability and user experience were explored through semistructured interviews with participants from both groups at 12 weeks (n=25). Results: Between September 2023 and September 2024, a total of 169 individuals were screened and 40 were enrolled (median age 66.5 years; 20 male individuals; median DHLS score: 4). Twenty-one participants were randomized to the Kidney Beam Ex-Tab group and 19 to the Kidney Beam alone group. Of the 40 participants, 35 (88%) completed the 12-week follow-up (intervention: n=18; control: n=17). All prespecified feasibility criteria for recruitment, retention, adherence, and safety were met. Qualitative findings indicated that the tablet loan and digital literacy training were acceptable and highly valued, enhancing confidence, motivation, and DHI engagement. Providing loaned devices was particularly important for overcoming access barriers, especially for participants unable to afford their own device. Conclusions: Providing Wi-Fi–enabled devices and digital literacy training alongside a DHI was feasible and acceptable for people with lower digital literacy levels. The findings support progression to a future definitive multicenter trial or implementation study and offer transferable insights for the design of digital inclusion strategies for other long-term health conditions. Trial Registration: ClinicalTrials.gov NCT04872933; https://clinicaltrials.gov/study/NCT04872933
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Feasibility and Acceptability of an eHealth-Based Physical Activity Coaching Intervention During Pulmonary Rehabilitation for People With Chronic Obstructive Pulmonary Disease: Mixed Methods Study

Background: Physical inactivity is a modifiable and significant trait in people with chronic obstructive pulmonary disease (COPD). While traditional exercise-based pulmonary rehabilitation (PR) improves symptoms and exercise tolerance, its impact on physical activity (PA) levels remains limited. Digital health (eHealth) interventions may help address this gap. Objective: This study aimed to assess the feasibility and acceptability of integrating an eHealth PA coaching intervention into PR for people with COPD. Methods: Patients enrolled in an outpatient PR program were recruited for a 3-week PA coaching intervention, which used a smart band connected to a mobile patient app and a web application for health care professionals (HCPs). The intervention included PA monitoring (steps per day); weekly goal setting; and app notifications for goal updates, achievement, and motivational messages. Weekly telephone calls supported goal adjustment and identification of PA barriers. The acceptability of the intervention was explored through a patient focus group. Results: Five patients with COPD (mean 67, SD 9 years; n=4, 80% female; mean predicted forced expiratory volume at 1 second of 49%, SD 23%) participated with 100% retention and adherence to the intervention (daily synchronization). No adverse events or PA barriers were identified. One patient reported an app connection issue that was resolved by restarting the app. Patients found the app easy to use and helpful for their PA awareness and remote monitoring by HCPs. Weekly goal adjustments and contact with an HCP were valued. Limitations regarding the app use included a lack of personalization, goal setting restricted to steps, and occasional step miscounts. Conclusions: The intervention was feasible and well accepted. Future studies with a larger sample are needed to assess the impact of the intervention on PA outcomes.
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AACR 2026 Chairs Identify Themes and Highlights from the Conference

The American Association for Cancer Research (AACR) Annual Meeting kicks off this weekend in San Diego. A whirlwind of sessions, keynotes, fireside chats, posters, and exhibitors, the meeting is THE annual event for the cancer community.

Before the conference, GEN spoke with AACR program chairs Paul S. Mischel, MD, Professor and Vice Chair for Research for the Department of Pathology at Stanford Medicine of Stanford University and Alice T. Shaw, MD, PhD, Chair of the Department of Medical Oncology and the Chief of Strategic Partnerships at Dana-Farber. In this interview, they share their perspectives on the event, what attendees should be looking out for, and what they, personally, are most looking forward to.

This interview has been edited for length and clarity.

 

GEN: What did you feel were some of the most important themes to include in the conference program?

Shaw: First of all, it’s been such an honor for me to work with Paul as well as our president, Lillian Siu, MD. We had an expert program committee and incredible staff at AACR who all helped shape the program.

This year’s annual meeting feels more meaningful than ever, because of everything going on in the world, including funding challenges, challenging geopolitics, and everything else. It has felt even more important that we have this time to bring together our global community of cancer researchers and investigators.

When Paul and I met last summer, we felt strongly that this meeting was not just about designing an incredibly strong scientific program to showcase the science and all of the innovation, but we wanted to make a point to demonstrate to the audience, and the world, the tangible benefits of scientific research to patients with cancer, and to highlight how all the research we do is done with an eye toward improving the lives of patients with cancer.

We intentionally planned a scientific program with patients and patient impact front and center and have tried to incorporate the patient perspective and even patient voices in some sessions—to emphasize that science drives impact for patients.

Mischel: When we started about a year ago, our conviction—that there probably has never been a more important year for an AACR meeting—grew over the year. This organization is a beacon of light at a time in which there’s been extraordinary progress in cancer, and [there is] the potential to really make a difference in patients’ lives at the face of some very major headwinds. What we’re seeing is a level of enthusiasm and engagement in coming together in the community that’s saying: we won’t be stopped in making a difference for patients with cancer. And there were a number of themes that were central to this meeting.

For example, precision—that you can use information about patients to identify what’s gone wrong and how to develop therapies based upon deep molecular knowledge. Partnership—The growing recognition of how we work together to make a difference for patients. It’s not a winner-take-all strategy. It’s not a race to the top for individuals. It’s a race to the top for people with cancer. And we do it effectively by joining hands to make a difference for patients. And global work—another major theme that we’re really talking about this year, because together we can make a real difference for people with cancer.

We work together with people that span an enormous range of disciplines and expertise. A number of themes came front and center during the year. The technologies to interrogate what’s happening in human beings, whether it’s in their tissue, their blood, or their images—it’s nothing short of breathtaking. The ability to either forestall cancer by detecting if it’s going to happen, or catch it early, or monitor our most effective treatments is really changing the game. New modalities for developing treatments. We’ve heard a lot about harnessing the immune system and about the development of small molecules. There’s all kinds of new chemistry, molecular glues and degraders that are leading the way. And they’re tied to deep investigations into the fundamental biology.

AI is changing the game as well. We are very excited that we’ve brought together perhaps the most interesting AI sessions that you can imagine, that talk about all of the ways that AI can be used—not like an oracle but actually in partnership with helping make a difference for patients, whether it be in the diagnostics or the development of therapeutics. AI is only beginning to be tapped to help us think about how to integrate knowledge across all of these domains. And it goes beyond that because it’s not only about the molecular composition of a person’s tumor, it’s about a human being, what they eat, where they live, what they do, and various other social determinants of health that might increase risks of cancer. A lot of attention is paid in the meeting to that aspect of it as well. So, I think we’re in for an incredibly interesting meeting.

Shaw: One of the themes that came right out from everyone on the program committee was how important it was to highlight AI; I think everyone believes that AI is going to be transformative and it’s going to impact all aspects of cancer research and clinical care in the coming years. We had a number of AI experts on our program committee. They really helped embed AI topics throughout the scientific and also the educational program.

In fact, when Paul and I were planning the opening plenary session, we really wanted one of the opening plenary speakers to be able to speak on AI. So, we have Regina Barzilay, PhD, from MIT, who’s going to speak on her work in the AI space, both in terms of drug discovery and all the way out to clinical applications. We also have an AI-focused plenary session all unto itself as well, to drive home the importance of AI tools and technologies. It is incredible how AI is already being used in terms of foundational discovery and in terms of real-world, clinical data mining and implementation. And Paul already mentioned genomics, precision medicine, biomarker discovery, histopathology, radiology, all of which are already being impacted by AI.

Mischel: One of the things that is perhaps most stunning is this idea that you might be able to prevent cancer. We already see real world examples of that with things like HPV vaccines. The work is advancing so quickly that it might be possible to build vaccines against [something] that might prevent people who are at high risk of developing cancer from getting those cancers. Our colleague and AACR President Lillian Siu, MD, has a presidential symposium focused on that. What I hope that we’re getting across is the real scale and power of the work that’s being presented and the way that it crosses so many disciplines at this meeting.

Shaw: We are going to have a large focus, as we usually do, on molecularly targeted therapies. We have several sessions on the basic research side, but also in the clinical trial sessions around targeting RAS. RAS, of course, is the most commonly mutated oncogene in human cancer and has been undruggable for decades.

In the last five to 10 years, we now finally have small molecule therapies that can target different RAS mutations. In fact, you may have just heard the news about a new RAS inhibitor, daraxonrasib from Revolution Medicines, and pivotal Phase III trial data in previously treated pancreatic cancer. This was an incredibly positive study, doubling overall survival. Not even knowing those results, though, we already had planned quite a lot around RAS.

In that context of precision therapies, I also want to mention that I’m excited about one of our discovery science plenaries on Saturday that is going to focus on minimal residual disease (MRD) in solid tumors. Here the question is, if we have such incredibly effective targeted therapies for oncogene-driven cancers like RAS, EGFR, and ALK, why aren’t we curing more patients who have these types of cancers? We believe that a lot of the reason is because we can’t eliminate every cancer cell. And if we could just understand what allows those residual cells to survive, perhaps we could eradicate those and then be on the road to curing patients who have advanced disease. So, this whole plenary will focus on the science around MRD and how that then leads to clinical applications as well.

Mischel: Fundamental science is deeply central to this process. We frame a lot of things in terms of what it means for patients’ lives. I think an important part of this meeting is also integrating how those discoveries really flow from the work in fundamental science. For example, in the opening plenary, we’re going to be hearing about how tumors change their stripes effectively to become resistant to treatments, the lineage plasticity, this idea that they adopt new states to become resistant. And then what can you do about it?

When people used to be diagnosed with terminal cancer, it meant that they were going to die soon, and now people can be diagnosed with terminal cancer and live for years. That’s stunning. And that is happening because of cancer research and the integration of cancer research all the way from the most mechanistic to the most applied. One of the deepest themes of this meeting comes into this concept of partnership, that we highlight the critical nature of each component and the integration of those components, all the way from fundamental discovery to translation to patients.

 

GEN: What are some of the biggest scientific challenges you’re seeing right now in cancer biology that you think people will be discussing at the meeting?

Mischel: Cancer is hard because it is evolution on steroids. The mechanism that I study—extrachromosomal DNA, the ability of cancer cells and tumors to change quickly to resist treatment—is all about that. And it comes from us; it’s our cells that have gone bad. We have to find ways to show how they’re different and target those differences. We’re getting better at it through our understanding of science.

Shaw:  I am someone who sits between basic research and the clinic, so I do a lot of translational research. What the AACR meeting does well is gets at this key challenge around how we translate basic discoveries into the clinic. We all just want better cancer therapies for our patients. There are many aspects that really make the translation of discoveries difficult, and these will come out in various forms at the meeting. We’ve been talking about how hard it is to understand the biology, and to identify and validate new targets for drug discovery, for cancer treatments in the future.

I have spent some time on the industry side, so I also recognize how challenging it is, even when you have what you think is a perfect target, to drug that target. At the annual meeting, we’re going to talk a lot about different modalities, ways of thinking about going after what we believe are important targets, be it a small molecule or maybe it’s a new degrader or maybe it’s some other very complicated biologic.

I want to emphasize that to use or to identify the optimal modality requires that we understand the biology and the science behind it. The other challenge that I’ve seen in the translational space is around identifying which patients are going to benefit from a new therapy. A good example of where we’ve seen struggles is immunotherapy and identifying novel immunotherapy combinations and which ones have robust activity. But we can’t tell exactly which patients are deriving that benefit. Oftentimes with no biomarker to guide us, we can’t move forward with what could be a promising combination. At the annual meeting, we try to highlight a lot of these correlative or translational biomarker studies from early phase clinical trials.

The last thing I’ll mention is around how we use preclinical models most effectively to predict what’s going to be a promising new therapy. Often, these models are just models; they’re simpler than human cancers. They can’t recapitulate the complexity of human biology, and they can lead us the wrong way. For example, to overestimate how effective a therapy may be. Fine-tuning our models and making them as predictive as possible is a key challenge.

Mischel: Data seems to suggest that very often you might need to combine agents to make differences for patients. And that of course makes enormous sense from a biological standpoint, but it’s much harder to do when you start thinking about how you design the trials to do that. It’s a slow process. And so, there is increasing recognition of the need to figure out how to combine agents and hopefully ways to figure out how practically to begin to test them more effectively and in a more cost-effective fashion.

 

GEN: What have been some of the biggest advances since the last meeting?

Mischel: I just keep coming back to RAS because it’s such a big deal. An undruggable target that we’re now seeing a huge change in. It’s a huge deal.

Shaw: I would agree with that. And it’s not simply the RAS inhibitor itself. Many of us believe that that is just the start of how we most effectively treat RAS-driven cancers. We need the best RAS inhibitor to serve as an anchor and then we will build these combinations around that which will hopefully be even more effective and allow us to maximally cytoreduce or debulk cancers and then allow us to take in other even higher order combinations.

We have sessions this year all around RAS-mutant cancers. We have a designated session just focused on pancreatic cancer biology, because understanding that biology well is going to be critical to developing these types of combination approaches.

The other thing that’s exciting—and this space is always evolving—is a plenary session on innovative new therapeutic modalities. This session will focus on a couple key modalities that are already transforming the space. Antibody-drug conjugates (ADC), for example. They are basically entering every therapeutic space that we have in cancer [and] understanding of the biology around how you’re targeting certain tumor-selective antigens.

Also, the design of the ADC itself can be very, very sophisticated and can be tweaked to further enhance activity. We’ll have some great talks around the next generation of ADCs that are going to be even more effective and even safer than what we currently have.

And in that same session around innovative modalities, we’ll also have talks around immune cell engagers; also, new data and next generation immune cell engagers that have built upon the early data with the first-generation immune cell engagers. The other very innovative new therapy that we will highlight, even in more detail than last year, is around radioligand therapies—a way to selectively target tumor cells with radiation. Unlike ADCs where the payload is chemotherapy, here the payload is radiation therapy. We’ve already seen really that these radioligand therapies are incredibly important for patients; they are coming out in all different therapeutic spaces. We thought it was important to highlight the latest advances in radioligand therapies, and we also have some education sessions so that physicians and scientists understand the basics around this innovative and exciting modality.

Mischel: The concepts of glues and degraders open the therapeutic landscape in a very different way. In many ways, the landscape has been limited to enzymes that you can inhibit, and not all good cancer targets are going to be enzymes that you can inhibit, and these glues and degraders change what you can do, whether it’s getting rid of them, moving them, giving them new functions. It’s a very powerful technology that is getting ready to make an enormous difference in clinic.

Shaw:  In the opening plenary session, George Winter will speak on glues and degraders. I also wanted to highlight the “New Drugs on the Horizon” sessions. We do this every year at the annual meeting. I love these sessions because they are first time disclosures of novel cancer therapies that have just entered the clinic or they’re about to enter the clinic. These talks go deep into the biology of the disease and how the drug was discovered and developed into early clinical plans. Several talks in this session this year are going to feature molecular glue degraders. That will be a nice way to tie together this theme around the degraders and the power of this new modality.

Mischel: One other thing I want to squeeze in is why on Earth are younger people getting cancer, particularly colorectal cancer? That’s really disturbing. We have sessions that are data rich that go right at that, and the answers are interesting.

 

GEN: Will there be any programming at the meeting that addresses the current state of funding?

Shaw:  We’re fortunate that Tony Letai, MD, PhD, the NCI director, is attending and speaking at the meeting in our opening ceremony on Sunday. He’s also participating in a workshop that we’re holding on grant writing and the scientific review process. On Monday, he will give an NCI director’s address and participate in a fireside chat where I’m sure he’s going to get a lot of questions around funding.

There are also sessions within the science and health policy track at the meeting that are going to focus on federal funding of grants. There is even a researcher town hall that’s really going to talk a lot about this.

 

GEN: Do you have any advice for young cancer researchers that may be attending AACR for the first time?

Mischel: I have two bits of advice. One of them is to know that what you’re doing is incredibly important. You are welcome. You’re one of us, you’re important. Do what you need and go forward because the work that you’re doing is going to matter an enormous amount. The second thing is do not be afraid. Do not think that the senior people at the meeting, the “bigwigs,” are too busy for you. Do not think they do not want to meet you, because they do. You’re the future. Go up, introduce yourself, say hello, tell us who you are.

 

GEN: What are things you are looking forward to outside of the sessions? 

Shaw:  I love the AACR annual meeting because it’s such an opportunity not just to learn, but to network and reconnect with friends and collaborators who you may not have seen in a while. I also think it’s a great venue for many of us to have formal sit-down meetings with industry partners and talk through the latest data that were just presented and discuss new collaborations. I personally am looking forward to the 5K race that Paul and I are speaking at. I’m going to try to run the race! One of my sons runs marathons and I thought, well, the least I can do is try and run a 5K.

Mischel: I’m looking forward to having a drink with Alice after the meeting ends and debriefing on putting this meeting together, which has been an absolute pleasure. I wish I were running the 5K race. I’m doing an education session at that time. I’m looking forward to meeting the students. There are these brilliant young people from all around the world and they’re just at the start of their career and they draw inspiration from this meeting, and I really enjoy it when they come up to me and I get to meet them. You see the brilliance and excitement in these people’s faces. And I’m looking forward to that.

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STAT+: Researchers behind GLP-1 obesity drugs advance new approach: Drop GLP-1 as a target

The scientists whose work spurred the development of powerful obesity drugs like Eli Lilly’s Zepbound are now raising a provocative hypothesis: Perhaps targeting the GLP-1 hormone is actually not necessary to achieve effective weight loss.

A group of researchers led by Richard DiMarchi and Matthias Tschöp has created an experimental drug that activates receptors of the GIP and glucagon hormones. They propose — based on rodent and monkey studies — that this kind of molecule, when administered at high enough doses, may result in weight loss comparable to the weight loss seen with drugs that include GLP-1 as a target, and without the tolerability issues like nausea and vomiting that often come with the approved treatments, according to a peer-reviewed draft paper published this week.

The research, funded by a biotech called BlueWater Biosciences, would still need to be confirmed in humans; oftentimes results seen in animals don’t translate in the clinic. But the proposed approach, outlined in the journal Molecular Metabolism by some of the most well-known scientists in the field, is likely to stir controversy, as it challenges a central notion underpinning not just the development of approved obesity products but also next-generation versions. 

Continue to STAT+ to read the full story…

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Landmark Pancreatic Cancer Trial Highlights Promise of RAS-Targeting Daraxonrasib

Earlier this week, Revolution Medicines reported positive results from a global Phase III trial of its RAS‑targeting inhibitor daraxonrasib (RMC-6236) in metastatic pancreatic ductal adenocarcinoma (PDAC). In the RASolute 302 trial, patients receiving daraxonrasib achieved longer progression‑free survival (PFS) and overall survival (OS) than those on standard cytotoxic chemotherapy.

The RASolute 302 trial enrolled patients with pancreatic tumors harboring a wide range of RAS variants, including those with RAS G12 mutations (such as G12D, G12V, and G12R), as well as those without an identified RAS mutation. The primary endpoints of the trial were PFS and OS in patients with tumors harboring RAS G12 mutations. Secondary endpoints assessed PFS and OS in all enrolled patients (the intent-to-treat population), including those with tumors with and without (wild type) an identified RAS mutation.

Daraxonrasib patients achieved a median OS of 13.2 months versus 6.7 months for chemotherapy. The drug was generally well tolerated, with a manageable safety profile and with no new safety signals.

“With these unprecedented results, daraxonrasib has the potential to achieve our goal of bending the mortality curve in pancreatic cancer. Unlike chemotherapy, daraxonrasib is a RAS-targeted medicine that targets RAS in its active ‘ON’ state, shutting down a key signaling pathway that drives aggressive tumor growth. This is especially important in pancreatic cancer, which is among the most RAS-driven cancers, with more than 90% of tumors harboring a RAS mutation that is the driver of the cancer,” asserted Mark A. Goldsmith, MD, PhD, CEO and chairman of Revolution Medicines.

Pancreatic cancer carries one of the highest mortality rates of any solid tumor, a consequence of late-stage diagnosis and resistance to standard chemotherapy. In the United States, recent estimates point to roughly 60,000 new cases and nearly 50,000 deaths each year. With most PDAC tumors driven by RAS alterations, the early success of emerging RAS‑targeted strategies hints at how much more may be possible as this therapeutic space continues to expand.

RAS is the key oncogenic driver of pancreatic cancer. Nearly all RAS mutations occur at KRAS position G12, but RAS mutations in other isoforms and at KRAS positions G13 and Q61 are also observed. Daraxonrasib works by suppressing RAS signaling through inhibition of the interaction between both wild-type and mutant RAS(ON) proteins and their downstream effectors.

Pancreatic cancer is the most RAS-addicted of all major cancers, with more than 90% of patients harboring tumors driven by mutations in RAS proteins. These mutations span a range of RAS variants that fuel aggressive tumor behavior. Daraxonrasib, a multi-selective inhibitor of RAS(ON) proteins, is the first investigational agent in a novel class of RAS inhibitors designed to address a diverse and broad spectrum of oncogenic RAS drivers.

“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life,” said Brian M. Wolpin, MD, MPH, professor of medicine at Harvard Medical School, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and principal investigator for the RASolute 302 trial. “The widely anticipated results of this study indicate that daraxonrasib provides a clear and highly meaningful step forward for patients with pancreatic cancer who have experienced progression on prior treatment, typically chemotherapy. I believe that this new approach is a very important advance for the field that I expect will be practice-changing for physicians and improve the care for patients with previously treated metastatic pancreatic cancer.”

Revolution Medicines now intends to submit the drug for approval by regulatory authorities, including the U.S. Food and Drug Administration as part of a future New Drug Application, and for presentation at the 2026 American Society of Clinical Oncology Annual Meeting. 

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