Purdue mRNA therapy delivery system proves to be shelf-stable, storable

The Proceedings of the National Academy of Sciences has published research about a Purdue University virus-mimicking platform technology that targets bladder cancer cells with mRNA therapies. The LENN platform scientists include, from left, Christina Ferreira, Saloni Darji, Bennett Elzey, Joydeep Rakshit, Feng Qu and David Thompson.
Photo Credit: Purdue University /Ali Harmeson

Scientific Frontline: "At a Glance" Summary

• Main Discovery: The LENN (Layer-by-layer Elastin-like Polypeptide Nucleic Acid Nanoparticle) platform successfully delivers mRNA therapies to bladder cancer cells while retaining full biological activity after being freeze-dried into a shelf-stable powder.
• Methodology: Researchers engineered a virus-mimicking dual-layer nanoparticle to condense and protect nucleic acids, then subjected the formulation to lyophilization (freeze-drying) and storage at -20°C to validate its stability and rehydration properties.
• Key Data: The lyophilized samples maintained complete structural integrity and functionality after three days of storage, successfully targeting upregulated receptors on tumor cells without triggering an immune response.
• Significance: This technology overcomes the severe cold-chain limitations of current lipid nanoparticle systems—which often require storage below -45°C—by providing a biomanufacturable, storable powder form that facilitates easier global distribution.
• Future Application: The team is upscaling the system for preclinical evaluation and initiating efficacy and safety studies in mouse models of bladder cancer.
• Branch of Science: Nanomedicine, Pharmaceutical Chemistry, and Oncology.
• Additional Detail: Multiple reaction monitoring (MRM) profiling confirmed that the system utilizes natural entry pathways and avoids immune detection, potentially solving the "redosing" clearance issues associated with traditional viral vectors.

“Recipe book” for reprogramming immune cells

Filipe Pereira, professor of molecular medicine at Lund University
Photo Credit: Courtesy of Lund University

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers at Lund University established a high-throughput screening platform and a library of over 400 immune-related transcription factors to decode the specific "recipes" required to reprogram accessible somatic cells into distinct immune cell identities.
• Methodology: The study utilized unique DNA barcodes attached to each transcription factor, allowing the simultaneous tracking of thousands of combinatorial possibilities to determine which specific factor groups drive conversion to desired immune lineages.
• Key Data: This four-year project successfully identified reprogramming protocols for six different immune cell types, including Natural Killer (NK) cells, which were previously impossible to generate through direct reprogramming.
• Context: Prior to this breakthrough, the specific reprogramming factors had been mapped for only four of the human body's more than 70 distinct immune cell types, limiting the development of synthetic immunotherapies.
• Significance: The platform enables the production of rare, patient-specific immune cells from abundant sources like skin fibroblasts, potentially expanding immunotherapy applications from cancer treatment to autoimmune diseases and regenerative medicine.

A bacterial toxin can counteract colorectal cancer growth

Sun Nyunt Wai
Photo Credit: Mattias Pettersson

Scientific Frontline: "At a Glance" Summary

• Discovery of Anti-Tumor Toxin: The purified cytotoxin MakA, secreted by the cholera bacterium Vibrio cholerae, has been identified as an agent that significantly inhibits the growth of colorectal cancer tumors.
• Mechanism of Action: MakA accumulates specifically within tumor tissue, inducing cancer cell death and suppressing proliferation while simultaneously recruiting innate immune cells, such as macrophages and neutrophils, to the tumor microenvironment.
• Safety and Specificity: In murine models, systemic administration of MakA targeted tumors locally without causing harmful systemic inflammation, weight loss, or organ dysfunction, indicating a high degree of specificity for cancerous tissue.
• Immune Modulation: The toxin alters the cellular composition of the tumor environment, stimulating the production of immune mediators that promote apoptosis while preserving regulatory mechanisms to protect surrounding healthy tissue.
• Therapeutic Potential: This study highlights a novel therapeutic avenue utilizing bacterial toxins to both directly target cancer cells and enhance the host's immune response, offering a potential alternative to traditional treatments like chemotherapy and radiation.

Intraoperative Tumor Histology May Enable More-Effective Cancer Surgeries

From left to right: Images of kidney tissue as detected with UV-PAM, as imaged by AI to mimic traditional H&E staining, and as they appear when directly treated with H&E staining.
Image Credit: Courtesy of California Institute of Technology

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers developed ultraviolet photoacoustic microscopy (UV-PAM) integrated with deep learning to perform rapid, label-free, subcellular-resolution histology on excised tumor tissue directly in the operating room.
• Mechanism: A low-energy laser excites the absorption peaks of DNA and RNA nucleic acids to generate ultrasonic vibrations; AI algorithms then process these signals to create virtual images that mimic traditional hematoxylin and eosin (H&E) staining without chemical processing.
• Key Data: The system achieves a spatial resolution of 200 to 300 nanometers and delivers diagnostic results in under 10 minutes (potentially under 5 minutes), effectively identifying the dense, enlarged nuclei characteristic of cancer cells.
• Context: Unlike standard pathology, which requires time-consuming freezing, fixation, and slicing that can damage fatty tissues like breast tissue, this method preserves sample integrity and eliminates preparation artifacts.
• Significance: This technology aims to drastically reduce re-operation rates—currently up to one-third for breast cancer lumpectomies—by allowing surgeons to confirm clean tumor margins intraoperatively across various tissue types (breast, bone, skin, organ).

Discovery on how aggressive breast cancer controls protein production

Three of the researchers behind the study, Kanchan Kumari Francesca Aguilo Margalida Esteva, Department of Molecular Biology.
Photo Credit: Mattias Pettersson

Scientific Frontline: "At a Glance" Summary

• Discovery: Researchers at Umeå University identified a novel mechanism in triple-negative breast cancer wherein the enzyme fibrillarin fine-tunes protein production to facilitate tumor growth and adaptation.
• Mechanism: Fibrillarin regulates the 2′-O-methylation (Nm) of ribosomal RNA and collaborates with the ribosomal protein RPS28 to construct specialized ribosomes with distinct translational capabilities.
• Specific Consequence: The depletion of fibrillarin causes a concurrent loss of RPS28, resulting in ribosomal heterogeneity—an imbalance of ribosome types that alters the proteome and drives oncogenic development.
• Context: This research shifts the understanding of cancer etiology beyond solely genetic mutations to include translational control, demonstrating how aggressive cells manipulate protein synthesis machinery.
• Implication: The findings suggest that targeting the ribosome assembly and modification machinery could serve as a new therapeutic strategy for treating aggressive cancers defined by misregulated protein production.

What Is: Organoid

Organoids: The Science and Ethics of Mini-Organs
Image Credit: Scientific Frontline / AI generated

The "At a Glance" Summary

• Defining the Architecture: Unlike traditional cell cultures, organoids are 3D structures grown from pluripotent stem cells (iPSCs) or adult stem cells. They rely on the cells' intrinsic ability to self-organize, creating complex structures that mimic the lineage and spatial arrangement of an in vivo organ.
• The "Avatar" in the Lab: Organoids allow for Personalized Medicine. By growing an organoid from a specific patient's cells, researchers can test drug responses on a "digital twin" of that patient’s tumor or tissue, eliminating the guesswork of trial-and-error prescriptions.
• Bridge to Clinical Trials: Organoids serve as a critical bridge between the Petri dish and human clinical trials, potentially reducing the failure rate of new drugs and decreasing the reliance on animal testing models which often fail to predict human reactions.
• The Ethical Frontier: As cerebral organoids (mini-brains) become more complex, exhibiting brain waves similar to preterm infants, science faces a profound question: At what point does biological complexity become sentience?

How Nutrient Availability Shapes Breast Cancer’s Spread

A microscope image of a breast cancer tumor (blue) and its surrounding microenvironment in a mouse model.
Image Credit: Joseph Szulczewski, David Inman, Kevin Eliceiri, and Patricia Keely/University of Wisconsin/National Institutes of Health

Scientists have gained new insights into how nutrient availability in different organs affects the spread, or metastasis, of breast cancer throughout the body.

In a study in mice jointly led by researchers at Harvard Medical School, Massachusetts General Hospital, and MIT, the team found that no single nutrient explains why breast cancer grows in one organ and not another. Instead, multiple nutrients and cancer cell characteristics work together to shape the spread of the disease.

The team also discovered that breast cancer cells require the nutrient purine to metastasize, regardless of their location or other nutrients available.

Study Underscores Role of Sleep in Reducing Toll of Social Adversity on Breast Cancer Survivors’ Health

Photo Credit: Ivan Oboleninov

Where someone lives can affect their health. For breast cancer survivors, their neighborhood can influence their recovery from treatment.

Researchers in UConn’s College of Liberal Arts and Sciences (CLAS) led a National Institutes of Health-funded study that found getting good sleep may buffer against the negative effects of living in a disadvantaged neighborhood, easing the transition from active treatment to survivorship.

Crystal Park, Board of Trustees Distinguished Professor in the Department of Psychological Sciences, and Keith Bellizzi, professor in the Department of Human Development and Family Sciences (HDFS), explored whether factors within breast cancer survivors’ control would influence recovery from treatment. Their findings were published in the peer-reviewed journal, Current Oncology.

Sleep has been found to enhance physical recovery and regulate inflammation, and this study is the first to show that poor sleep may exacerbate the health impact of residential hardship among breast cancer survivors.

When ovarian cancer alters the abdominal cavity

Metastases from ovarian cancer in the abdominal cavity: Cancer cells alter the tissue of the omentum in such a way that it supports their spread.
Image Credit: Scientific Frontline / stock image

Ovarian cancer often forms secondary tumors, especially in a certain tissue in the abdominal cavity known as the omentum. Researchers from the University of Basel and University Hospital Basel have investigated what happens when the cancer “hijacks” this organ. It is hoped their findings will lead to more successful treatments. 

Ovarian cancer often goes undetected for a long time. In seven out of 10 patients, the tumor has already formed secondary tumors in the abdominal cavity at the time of diagnosis. These metastases are particularly common in a tissue called the omentum, also known as the peritoneal apron. This organ is located in front of the intestine, performs protective and immune functions, and harbors fat cells. 

“In advanced ovarian cancer, the question arises as to whether, in addition to the visible tumors and metastases, the omentum should also be completely removed as a preventive measure in order to reduce the recurrence of tumors,” explains Dr. Francis Jacob from the Department of Biomedicine at the University of Basel and the University Hospital Basel. 

Researchers find breast cancer drug boosts leukemia treatment

Jeffrey Tyner, Ph.D., and Melissa Stewart, Ph.D., led a team at OHSU that discovered a new drug combination that may help people with acute myeloid leukemia.
Photo Credit: OHSU/Christine Torres Hicks

A research team at Oregon Health & Science University has discovered a promising new drug combination that may help people with acute myeloid leukemia overcome resistance to one of the most common frontline therapies.

In a study published in Cell Reports Medicine, researchers analyzed more than 300 acute myeloid leukemia, or AML, patient samples and found that pairing venetoclax, a standard AML drug, with palbociclib, a cell-cycle inhibitor currently approved for breast cancer, produced significantly stronger and more durable anti-leukemia activity than venetoclax alone. The findings were confirmed in human tissue samples as well as in mouse models carrying human leukemia cells.

“Of the 25 drug combinations tested, venetoclax plus palbociclib was the most effective. That really motivated us to dig deeper into why it works so well, and why it appears to overcome resistance seen with current therapy,” said Melissa Stewart, Ph.D., research assistant professor in the OHSU School of Medicine and Knight Cancer Institute and lead author of the study.

More than 20,000 Americans are diagnosed with AML each year, making it one of the most common types of leukemia — and one of the most aggressive.

Machine learning drives drug repurposing for neuroblastoma

Daniel Bexell leads the research group in molecular pediatric oncology, and Katarzyna Radke, first author of the study.
Photo Credit: Lund University

Using machine learning and a large volume of data on genes and existing drugs, researchers at Lund University in Sweden have identified a combination of statins and phenothiazines that is particularly promising in the treatment of the aggressive form of neuroblastoma. The results from experimental trials showed slowing of tumor growth and higher survival rates. 

The childhood cancer, neuroblastoma, affects around 15-20 children in Sweden every year. Most of them fell ill before the age of five. Neuroblastoma is characterized by, among other things, tumors that are often resistant to drug treatment, including chemotherapy. The disease exists in both mild and severe forms, and the Lund University researchers are mainly studying the aggressive form, high-risk neuroblastoma. This variant is the form of childhood cancer with the lowest survival rate. 

Oncology: In-Depth Description

Image Credit: Scientific Frontline / AI generated

Oncology is the branch of medicine and biology dedicated to the study, diagnosis, treatment, and prevention of cancer. Derived from the Greek word onkos (meaning "mass" or "bulk"), this field focuses on understanding neoplasms (tumors) and the complex biological mechanisms that cause uncontrolled cell division. The primary goal of oncology is to improve patient survival and quality of life through the development of therapeutic interventions and the early detection of malignancies.

Dresden Research Group Uncovers New Key Mechanism in Cancer Cells

The research group led by Dr. Mohamed Elgendy (4th from left).
Photo Credit: © MSNZ

A study by the Mildred Scheel Early Career Center group led by Dr. Mohamed Elgendy at the TUD Faculty of Medicine provides fundamental insights into cancer biology. Published in the renowned journal Nature Communications, the study shows for the first time that the protein MCL1 not only inhibits programmed cell death but also plays a central role in tumor metabolism. 

The researchers have succeeded in tracing two classic hallmarks of cancer – the evasion of apoptosis (a form of programmed cell death) and the dysregulation of energy metabolism – back to a common molecular mechanism. 

Stanford Medicine study identifies immune switch critical to autoimmunity, cancer

Edgar Engleman, MD, professor of pathology
Photo Credit: Courtesy of Stanford School of Medicine

A single signaling pathway controls whether immune cells attack or befriend cells they encounter while patrolling our bodies, researchers at Stanford Medicine have found. Manipulating this pathway could allow researchers to toggle the immune response to treat many types of diseases, including cancers, autoimmune disorders and those that require organ transplants.

The research, which was conducted in mice, illuminates the mechanism of an important immune function that prevents inappropriate attacks on healthy tissue. Called peripheral immune tolerance, the key cellular players, known as regulatory T cells (or Tregs, pronounced “tee-regs”), were first described in the late 1990s in a series of discoveries that were recently recognized with the 2025 Nobel Prize in physiology or medicine.

A platform to test new cancer treatments

Differentiated hepatic cells growing in a flask re-gain the appearance of cells present in liver.
Image Credit: © FAMOL, UNIGE

Overcoming acquired treatment resistance is one of the major challenges in the fight against cancer. While combination therapies hold promise, their toxicity to healthy tissue remains a major hurdle. To anticipate these risks, researchers at the University of Geneva (UNIGE) have developed in vitro models of the kidneys, liver, and heart – three organs particularly sensitive to such therapies. This fast, animal-free approach paves the way for safer evaluation of new treatments. The findings are published in Biomedicine & Pharmacotherapy. 

Recent advances in immunotherapy, targeted therapies, and gene therapies have significantly improved survival rates for patients with cancer. However, over time, many tumors develop resistance to these treatments, undermining their effectiveness. This phenomenon, known as ‘acquired resistance’, has become one of the major challenges in oncology. 

UCLA team discovers how to target ‘undruggable’ protein that fuels aggressive leukemia

B-lymphoblastic leukemia, a type of blood cancer.
Image Credit: Courtesy of the Rao Laboratory.

Researchers at the UCLA Health Jonsson Comprehensive Cancer Center have identified a small molecule that can inhibit a cancer-driving protein long considered impossible to target with drugs — a discovery that could open the door to a new class of treatments for leukemia and other hard-to-treat cancers. 

The compound, called I3IN-002, disrupts the ability of a protein known as IGF2BP3 to bind and stabilize cancer-promoting RNAs, a mechanism that fuels aggressive forms of acute leukemia. The study published in the journal Haematologica, found the molecule not only slowed leukemic cell growth but also triggered cancer cell death and reduced the population of leukemia-initiating cells that sustain the disease.

“This project has been more than a decade in the making,” said Dr. Dinesh Rao, professor of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA and senior author of the study. “We discovered IGF2BP3 years ago as an important driver in acute leukemias, and for a long time there were no tools to target it. To finally show that we can inhibit this protein and disrupt its function in cancer cells is incredibly exciting.” 

Prognostic tool could help clinicians identify high-risk cancer patients

In a new study, MIT researchers and their collaborators identified a practical, powerful predictor that could help clinicians spot high-risk lymphoma patients early and tailor treatments to improve survival.
Image Credit: Scientific Frontline / stock image

Aggressive T-cell lymphoma is a rare and devastating form of blood cancer with a very low five-year survival rate. Patients often relapse after receiving initial therapy, making it especially challenging for clinicians to keep this destructive disease in check.

In a new study, researchers from MIT, in collaboration with researchers involved in the PETAL consortium at Massachusetts General Hospital, identified a practical and powerful prognostic marker that could help clinicians identify high-risk patients early, and potentially tailor treatment strategies to improve survival.

The team found that, when patients relapse within 12 months of initial therapy, their chances of survival decline dramatically. For these patients, targeted therapies might improve their chances for survival, compared to traditional chemotherapy, the researchers say.

UCLA study uncovers how a key protein helps breast cancer cells survive in hostile conditions

NBCn1 (purple) sits in the cell membrane and brings two sodium ions (2Na⁺) and one carbonate ion (CO₃²⁻) into the cell, raising its internal pH. This helps breast cancer cells stay alkaline and survive in low-oxygen, acidic tumor environments.
Illustration Credit: Courtesy of UCLA/Health

UCLA scientists have characterized the structure and function of a key survival protein in breast cancer cells that helps explain how these tumors resist environmental stress and thrive in acidic, low-oxygen environments that would normally be toxic to healthy cells.

Breast cancer cells rely on a transporter protein called NBCn1 to bring alkali ions into the cell and maintain a favorable internal pH. Using advanced cryo-electron microscopy combined with computational modeling, the researchers showed that NBCn1 moves two sodium ions and one carbonate ion through an efficient “elevator-like” motion that minimizes energy use. This allows NBCn1 to achieve a high transport rate of approximately 15,000 ions per second, helping tumor cells maintain an internal pH that promotes survival, division and resistance to acidic stress. 

The shape of the cell nucleus influences the success of cancer treatment

Photo Credit: Thor Balkhed

Cancer cells with a cell nucleus that is easily deformed are more sensitive to drugs that damage DNA. These are the findings of a new study by researchers at Linköping University. The results may also explain why combining certain cancer drugs can produce the opposite of the intended effect. The study has been published in the journal Nature Communications. 

A few years ago, a new type of drug was introduced that exploits deficiencies in cancer cells’ ability to repair damage to their DNA. These drugs, called PARP1 inhibitors, are used against cancers that have mutations in genes involved in DNA repair, such as the breast cancer gene 1 (BRCA1). This gene has such a central role in the cell’s ability to repair serious DNA damage that mutations in it greatly increase the risk of developing cancer, often at a young age. The risk is so high that some women with a mutated BRCA1 gene choose to have their breasts and ovaries surgically removed to prevent cancer. 

Immune cells turn damage into repair

Intestines one week after abdominal irradiation, showing proliferating epithelial cells (in brown).
Image Credit: Julius Fischer / TUM 

Patients receiving intensive cancer treatments often suffer from severe damage to the intestinal lining. Researchers from the Technical University of Munich (TUM) and the Leibniz Institute for Immunotherapy (LIT) have discovered that certain immune cells can trigger healing processes. They use inflammatory signals to do so - which is surprising, as inflammation in the intestine was previously thought to be primarily harmful. This finding could open new possibilities for therapies. 

Regulatory T cells (Tregs), a specialized type of immune cells, are usually seen as “peacekeepers” that prevent excessive immune attacks. In a study  published in Signal Transduction and Targeted Therapy, researchers from the Department of Radiation Oncology at the TUM University Hospital and the LIT Cooperation Group “Innate Immune Sensing in Cancer and Transplantation” uncovered how the body's own immune system can be harnessed to repair the intestinal lining and improve survival.