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Brain Tumor

Unlocking Lung Cancer Treatment: Discovery of Master Regulator Blocks Immunotherapy Response

Researchers have discovered that ‘DEAD-box helicases 54 (DDX54)’, a type of RNA-binding protein, is the master regulator that hinders the effectiveness of immunotherapy — opening a new path for lung cancer treatment.

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Unlocking Lung Cancer Treatment: Discovery of Master Regulator Blocks Immunotherapy Response

Lung cancer is one of the most aggressive types of cancer, accounting for a significant number of cancer-related deaths worldwide. Despite advances in treatment options like immunotherapy, fewer than 20% of patients respond to these treatments. This highlights the urgent need for new strategies tailored to both responders and non-responders.

Researchers at KAIST have made a groundbreaking discovery that sheds light on this issue. They identified ‘DEAD-box helicases 54 (DDX54)’, a type of RNA-binding protein, as the master regulator that hinders the effectiveness of immunotherapy. This breakthrough technology has been transferred to faculty startup BioRevert Inc., where it is currently being developed as a companion therapeutic and expected to enter clinical trials by 2028.

The research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering demonstrated that suppressing DDX54 enhances immune cell infiltration into tumors and significantly improves the efficacy of immunotherapy. This study is especially significant in that it successfully demonstrated that suppressing DDX54 in immune-desert lung tumors can overcome immunotherapy resistance and improve treatment outcomes.

The team used transcriptomic and genomic data from immune-evasive lung cancer patients to infer gene regulatory networks through systems biology techniques. They identified DDX54 as a central regulator in the immune evasion of lung cancer cells. In a syngeneic mouse model, the suppression of DDX54 led to significant increases in the infiltration of anti-cancer immune cells such as T cells and NK cells, and greatly improved the response to immunotherapy.

Single-cell transcriptomic and spatial transcriptomic analyses further showed that combination therapy targeting DDX54 promoted the differentiation of T cells and memory T cells that suppress tumors, while reducing the infiltration of regulatory T cells and exhausted T cells that support tumor growth. The mechanism is believed to involve DDX54 suppression inactivating signaling pathways such as JAK-STAT, MYC, and NF-κB, thereby downregulating immune-evasive proteins CD38 and CD47.

This discovery has significant implications for lung cancer treatment. By targeting the master regulator DDX54, clinicians can induce responsiveness to immunotherapy in previously resistant cancers, ultimately improving treatment outcomes for patients.

The study was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 2, 2025, with Jeong-Ryeol Gong being the first author, Jungeun Lee a co-first author, and Younghyun Han a co-author of the article. This work was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Research Program and Basic Research Laboratory Program.

Brain Tumor

AI Tool Tracks Lung Tumors as You Breathe, Potentially Saving Lives

An AI system called iSeg is reshaping radiation oncology by automatically outlining lung tumors in 3D as they shift with each breath. Trained on scans from nine hospitals, the tool matched expert clinicians, flagged cancer zones some missed, and could speed up treatment planning while reducing deadly oversights.

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The article describes how a team of Northwestern Medicine scientists has developed an innovative AI tool called iSeg that can accurately outline lung tumors on CT scans, even as they move with each breath. This is a critical factor in planning radiation treatment, which half of all cancer patients in the US receive during their illness. The study found that iSeg consistently matches expert outlines across hospitals and scan types, and also flags additional areas that some doctors may miss – areas linked to worse outcomes if left untreated.

The AI tool was trained using CT scans and doctor-drawn tumor outlines from hundreds of lung cancer patients treated at nine clinics within the Northwestern Medicine and Cleveland Clinic health systems. The study’s authors believe that iSeg can help reduce delays, ensure fairness across hospitals, and potentially identify areas that doctors might miss – ultimately improving patient care and clinical outcomes.

The research team is now testing iSeg in clinical settings, comparing its performance to physicians in real time. They are also integrating features like user feedback and working to expand the technology to other tumor types, such as liver, brain, and prostate cancers. The team envisions this as a foundational tool that could standardize and enhance how tumors are targeted in radiation oncology.

The study was published today (June 30) in the journal npj Precision Oncology.

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Brain Injury

The Hidden Glitch Behind Hunger: Scientists Uncover the Brain Cells Responsible for Meal Memories

A team of scientists has identified specialized neurons in the brain that store “meal memories” detailed recollections of when and what we eat. These engrams, found in the ventral hippocampus, help regulate eating behavior by communicating with hunger-related areas of the brain. When these memory traces are impaired due to distraction, brain injury, or memory disorders individuals are more likely to overeat because they can’t recall recent meals. The research not only uncovers a critical neural mechanism but also suggests new strategies for treating obesity by enhancing memory around food consumption.

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The Hidden Glitch Behind Hunger: Scientists Uncover the Brain Cells Responsible for Meal Memories

Imagine forgetting about lunch and suddenly feeling extremely hungry. It’s a common phenomenon that can lead to overeating and disordered eating behaviors. Researchers have now identified a specific group of brain cells called “meal memory” neurons in laboratory rats that could explain why people with memory problems often overeat.

These specialized cells, found in the ventral hippocampus region of the brain, become active during eating and form what scientists call “meal engrams” – sophisticated biological databases that store information about food consumption experiences. An engram is essentially the physical trace a memory leaves behind in the brain, making it possible for us to recall specific details about our meals.

The discovery has significant implications for understanding human eating disorders. Patients with memory impairments, such as those with dementia or brain injuries that affect memory formation, may often consume multiple meals in quick succession because they cannot remember eating. Furthermore, distracted eating – such as mindlessly snacking while watching television or scrolling on a phone – may impair meal memories and contribute to overconsumption.

Researchers used advanced neuroscience techniques to observe the brain activity of laboratory rats as they ate, providing the first real-time view of how meal memories form. They found that meal memory neurons are distinct from other types of brain cells involved in memory formation. When these neurons were selectively destroyed, lab rats showed impaired memory for food locations but retained normal spatial memory for non-food-related tasks.

The study revealed that meal memory neurons communicate with the lateral hypothalamus, a brain region long known to control hunger and eating behavior. When this hippocampus-hypothalamus connection was blocked, the lab rats overate and could not remember where meals were consumed.

The findings have immediate relevance for understanding human eating disorders and could eventually inform new clinical approaches for treating obesity and weight management. Current weight management strategies often focus on restricting food intake or increasing exercise, but the new research suggests that enhancing meal memory formation could be equally important.

“We’re finally beginning to understand that remembering what and when you ate is just as crucial for healthy eating as the food choices themselves,” said Scott Kanoski, professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences and corresponding author of the study.

In addition to understanding human eating disorders, this research could also inform new strategies for treating obesity and weight management. Current approaches often focus on restricting food intake or increasing exercise, but the new findings suggest that enhancing meal memory formation could be equally important.

By uncovering the brain cells responsible for meal memories, scientists have taken a significant step towards understanding the complex relationships between our brains, bodies, and eating habits. The discovery of these specialized neurons offers new hope for developing effective treatments and interventions to help individuals manage their weight and improve their overall health.

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Brain Tumor

Uncovering Nature’s Secret: Ginger Compound Shows Promise in Targeting Cancer Cells’ Metabolism

Scientists in Japan have discovered that a natural compound found in a type of ginger called kencur can throw cancer cells into disarray by disrupting how they generate energy. While healthy cells use oxygen to make energy efficiently, cancer cells often rely on a backup method. This ginger-derived molecule doesn t attack that method directly it shuts down the cells’ fat-making machinery instead, which surprisingly causes the cells to ramp up their backup system even more. The finding opens new doors in the fight against cancer, showing how natural substances might help target cancer s hidden energy tricks.

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The quest for a cure to cancer has led scientists to explore the depths of nature, seeking answers that can unlock the secrets of this complex disease. One such natural compound is found in kencur ginger, which has shown promise in targeting the metabolic pathway of cancer cells.

In normal human cells, energy is produced through the oxidation of glucose, resulting in the production of ATP (adenosine triphosphate), the primary energy source necessary for life. However, cancer cells take a different approach, using glycolysis to produce ATP even when oxygen is present. This inefficient method, known as the Warburg effect, has puzzled scientists, leading them to wonder why cancer cells choose this pathway.

Associate Professor Akiko Kojima-Yuasa and her team at Osaka Metropolitan University’s Graduate School of Human Life and Ecology have been investigating the cinnamic acid ester ethyl p-methoxycinnamate, a main component of kencur ginger. Their previous research revealed that this compound has inhibitory effects on cancer cells. The team decided to further their study by administering the acid ester to Ehrlich ascites tumor cells, which resulted in some unexpected findings.

The researchers discovered that ethyl p-methoxycinnamate not only disrupts de novo fatty acid synthesis and lipid metabolism but also triggers increased glycolysis as a possible survival mechanism in the cells. This adaptability was theorized to be attributed to the compound’s inability to induce cell death.

“These findings not only provide new insights that supplement and expand the theory of the Warburg effect, which can be considered the starting point of cancer metabolism research, but are also expected to lead to the discovery of new therapeutic targets and the development of new treatment methods,” stated Professor Kojima-Yuasa.

The study’s results have significant implications for cancer research, opening up new avenues for investigation into the metabolic pathways of cancer cells. As scientists continue to explore the mysteries of nature, they may uncover even more secrets that can lead to a deeper understanding and potential cures for this complex disease.

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