Targeted alpha therapy: Breakthrough in treating refractory skin cancer

Metastatic melanoma, also known as stage IV melanoma, is a type of skin cancer that spreads to other parts of the body. It is one of the most aggressive forms of skin cancer, with current therapies — including immunotherapy and targeted drugs — showing limited effectiveness. Radiotherapy is an emerging treatment for melanoma, but conventional beta-emitting radionuclide therapies have limitations due to their low energy transfer and long-range radiation, which can cause unintended damage to healthy tissues.

To enhance the efficacy of radiotherapy, a research team from Japan, led by Assistant Professor Hiroyuki Suzuki from Chiba University, including Dr. Tomoya Uehara from Chiba University, Dr. Noriko S. Ishioka from National Institutes for Quantum Science and Technology, Dr. Hiroshi Tanaka from Juntendo University, Dr. Tadashi Watabe from Osaka University, adopted targeted alpha therapy (TAT) as a promising alternative to conventional beta therapy. They developed an astatine-211 (211At)-labeled peptide drug that could offer a potential breakthrough for treating metastatic melanoma. The research was conducted in collaboration with the National Institutes for Quantum Science and Technology and was published in the European Journal of Nuclear Medicine and Molecular Imaging on January 20, 2025.

TAT is a form of radiotherapy that involves drugs labeled with alpha particle-emitting radioisotopes. Compared to other forms of radioactive emissions (beta and gamma emissions), alpha particles are heavier and therefore have a short range. Owing to their greater mass, alpha particles also carry relatively higher energy, which is beneficial for the disruption of cancer cells.

To develop the treatment, the researchers first identified an optimal hydrophilic linker to enhance tumor targeting and reduce off-target accumulation. The team then designed an astatine-211(211At)-labeled α-melanocyte-stimulating hormone (α-MSH) peptide analog called [211At]NpG-GGN4c to specifically target melanocortin-1 receptors (MC1R), which are overexpressed in melanoma cells. “Since the tagged peptide was also receptor-targeted, it allowed for a high tumor selectivity while minimizing radiation exposure to the surrounding tissues,” comments Dr. Suzuki.

The synthesized peptides were then tested on B16F10 melanoma-bearing mice models, following which they conducted a biodistribution analysis where the team compared tumor uptake, clearance from organs, and the overall stability of the compound. Dr. Uehara elaborates on the methodology, saying, “We treated the mice with different doses of the compound while monitoring the tumor response, body weight, and survival rates over time. We found a dose-dependent inhibitory effect in a melanoma-bearing mouse model, confirming the effectiveness of our approach.”

The findings were remarkable. The [211At]NpG-GGN4c showed high accumulation in tumors and rapid clearance from non-target organs, confirming its specificity for MC1R on melanoma cells. Monitoring tumor growth revealed significant tumor suppression in a dose-dependent manner. Furthermore, [211At]NpG-GGN4c also demonstrated high stability in blood plasma, minimizing the risk of radioactive leakage in the body.

Hailing the exciting results, Dr. Suzuki affirms that the molecular design of their synthesized drug could be useful for developing other 211At-labeled radiopharmaceuticals. He says, “We believe our approach could open up new possibilities for treating refractory cancers beyond melanoma.”

The team is also hopeful about promoting a clinical application of 211At-based TAT. “If successfully translated into human trials, this therapy may emerge as a viable treatment option for patients with advanced melanoma in the coming years,” speculates Dr. Suzuki. “This could provide new therapeutic opportunities for patients with refractory cancer.”

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Blind to the burn: Misconceptions about skin cancer risk in the US

Skin cancer is the most common cancer in the United States and a significant health issue, with millions of non-melanoma cases and tens of thousands of melanomas diagnosed annually. Furthermore, treating skin cancer costs the U.S. approximately $8.9 billion annually.

Those with fair skin, a history of sun exposure or tanning bed use, and a genetic predisposition, are at higher risk. Key barriers to prevention include a lack of awareness, cultural preferences for tanned skin, and limited access to sun protection.

A study by researchers at Florida Atlantic University’s Charles E. Schmidt College of Medicine is one of a few to explore associations between reported number of sunburns and sociodemographic characteristics, in addition to examining prevalence of protective skin behaviors adopted by the U.S. adult population in a nationally representative sample. According to the American Academy of Dermatology, experiencing five or more blistering sunburns between ages 15 and 20 increases one’s melanoma risk by 80% and nonmelanoma skin cancer risk by 68%.

Using data from the U.S. National Cancer Institute’s 2022 Health Information National Trends Survey 6 (HINTS 6), researchers selected questions focused on respondents’ confidence in their health, perceived cancer risk, and worry about getting diagnosed with cancer, as well as their sunburn experiences over the past year. Sociodemographic factors that were studied included age, gender, occupational status, marital status, educational level, Hispanic origin, race and income due to their potential link to skin cancer risk.

Among 6,252 participants surveyed, when asked how confident they felt about their ability to take good care of their own health, most respondents felt either very confident (44%) or completely confident (27.3%). Findings, published in the American Journal of Lifestyle Medicine, also showed most respondents had moderate concerns about skin cancer risk. Only 9.1% reported being extremely worried, while the majority were either somewhat (26.6%) or slightly (25.6%) concerned.

For sunburn and skin protection, 67.6% reported no sunburns in the past year, while 30.3% had 1-5 sunburns. Additionally, 6.4% reported consuming alcohol while sunburned, a known risk factor for increased sunburn incidence. Activities like drinking alcohol, working outside or swimming were common among those who reported sunburns.

Using multinomial regression analysis, statistically significant associations were reported between the number of sunburns and sociodemographic factors. Adults (over 40) had lower sunburn risks, as did women. Disabled, unemployed, and multi-occupation participants reported fewer sunburns. Married or partnered individuals had higher risks of sunburn, while divorced or single participants had lower risks. Higher education levels, being Hispanic, Black, Asian or of mixed race were linked to lower sunburn risks. Higher income groups had significantly higher risks of sunburns, with the highest income group being more than four times more likely to report a sunburn.

“Social determinants such as race/ethnicity, sex, income and employment status are closely linked to sunburn and skin cancer risk,” said Lea Sacca, Ph.D., senior author and an assistant professor in the Department of Population Health and Social Medicine, within the Schmidt College of Medicine. “While Hispanics and Black Americans generally report lower rates of sunburn, Hispanics often perceive greater benefits of UV exposure, which increases their risk. Factors such as sex, education, and income also influence sunscreen use, with lower use observed among Black Americans and Hispanic Americans. However, within these groups, women with higher education and income are more likely to use sunscreen. Interestingly, higher income is associated with more frequent sunburns.”

Skin cancer includes three main types: basal cell carcinoma, squamous cell carcinoma and melanoma. Basal cell carcinoma is the most common and least aggressive, typically appearing as a shiny, pearly bump or pinkish patch, often on sun-exposed areas. Squamous cell carcinoma usually appears as red, scaly patches or open sores and can spread to other parts of the body if not treated early. Melanoma, the most dangerous form, develops in pigment-producing cells (melanocytes) and can appear as a new mole or changes to an existing one. It is highly aggressive and can spread quickly to other organs if not caught early.

“Understanding perceptions of skin cancer risk and the prevalence of protective behaviors is vital to reducing the likelihood of developing skin cancer, particularly among vulnerable groups,” said Madison Etzel, first author and a second-year medical student in the Schmidt College of Medicine. “Our study underscores the importance of raising awareness about skin cancer susceptibility as we found that all sociodemographic factors were significantly linked to the number of reported sunburns in the past year. Future research should explore how additional social determinants of health influence sunburn incidence and prevention behaviors. A deeper understanding of these factors is critical to addressing the widespread harms of skin cancer in U.S. adults.”

According to the American Cancer Society and other health organizations, practicing sun safety and skin awareness is vital to preventing skin cancer. Regularly applying a broad-spectrum sunscreen with an SPF of 30 or higher, especially when spending time outdoors, and reapplying every two hours is essential as a first step for skin cancer prevention. Avoiding direct sunlight, particularly between 10 a.m. and 4 p.m., when UV rays are strongest, and seeking shade whenever possible are also additional preventive strategies to consider to reduce the risk of this disease. Moreover, protecting skin further by wearing long-sleeve clothing, wide-brimmed hats and sunglasses with 100% UVA/UVB protection has also been recommended. It’s also crucial to avoid tanning beds, as they increase the risk of skin cancer.

Regular self-exams of the skin for any unusual moles or changes, along with professional skin screenings by a dermatologist, can help with early detection. Surfaces like water, sand and snow also can reflect UV rays, so reapply sunscreen more frequently in these environments. Finally, staying hydrated supports skin health and resilience against UV damage.

Study co-authors are Nada Eldawy; Sahar Kaleem; Austin Lent; Adrienne Dean; Ayden Dunn; Paige Brinzo; and Samantha Jimenez, all medical students in the Schmidt College of Medicine.

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Sons worst affected by smoking in pregnancy – study

Data from half-a-million people was assessed by the University of Aberdeen research team.

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Doctors try to stop under-eights drinking slushies

Paediatricians studied 21 children in the UK and Ireland who became very ill after the icy drinks.

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Children under eight should avoid drinking slushies, doctors warn

Paediatricians studied 21 children in the UK and Ireland who became very ill after the icy drinks.

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NHS to offer take-at-home tablet for MS

Broadening access to cladribine should help more patients avoid hospital and free up clinic time.

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Nature-inspired 3D-printing method shoots up faster than bamboo

Charging forward at top speed, a garden snail slimes up 1 millimeter of pavement per second. By this logic, Beckman Institute for Advanced Science and Technology researchers’ new 3D printing process speeds past existing methods — at a snail’s pace.

Researchers in Beckman’s Autonomous Materials Systems Group created “growth printing,” which mimics tree trunks’ outward expansion to print polymer parts quickly and efficiently without the molds and expensive equipment typically associated with 3D printing. Their work appears in the journal Advanced Materials.

“Humans are incredibly talented at making things. Completely new manufacturing processes are hard to find. Growth printing is entirely new, which is thrilling,” said Sameh Tawfick , a professor of mechanical science and engineering at the University of Illinois Urbana-Champaign and project lead.

Tawfick said the most common industrial manufacturing technology is injection molding, where molten polymers take shape in a metal mold. Though effective for mass production, maintaining the molds and curing ovens (where the plastic hardens) can be cost-prohibitive and unwieldy — especially for large objects like boat hulls or fan blades. Additive manufacturing, which prints 3D objects like a layer cake, is mold-less and ideal for custom parts like prosthetics.

“Polymer 3D printing equipment has matured, but there are still aspects that make it expensive and very slow,” Tawfick said. “Our goal was to increase the manufacturing speed, size and material quality while maintaining a low cost. This process that we came up with is truly fast and inexpensive.”

First, Sameh and his colleagues pour amber-colored liquid resin called dicyclopentadiene, or DCPD, into an open glass container submerged in ice water. They heat a center point in the resin to 70C. As the reaction takes over, heat radiates outward from the original point of contact at 1 mm/s, more than 100 times faster than the desktop 3D printers available for home use and 60 times faster than the world’s fastest-growing species of bamboo. Everything the heat touches hardens into a growing sphere, like if the mythical King Midas seized the Earth’s core. Self-sustained by heat’s steady release, the reaction — called frontal ring-opening metathesis polymerization and nicknamed FROMP — uses minimal energy to harden the resin into its solid form: poly- dicyclopentadiene, or p-DCPD.

As the hardened sphere grows, the researchers alter its shape by pulling it out of the resin like an apple out of gooey caramel. Since the liquid-to-solid reaction only happens below the surface, the researchers can lift, dip or spin the solid part like blown glass to manipulate its size and shape. For example: to create a corrugated, or wavy, edge, the researchers lift the resin slightly, hold it still, and repeat.

The researchers designed their process to mimic how a tree steadily expands outward, ring by ring. In nature, elements like gravity, wind and temperature complement and complicate a tree’s tendency to grow symmetrically, resulting in trees that bow in the wind or reach toward a patch of sunlight in the forest canopy.

Tawfick became enamored of living organisms’ growth patterns and resulting shapes — also known as morphogenesis — upon reading D’Arcy Wentworth Thompson’s book, “On Growth and Form.” Last August, when Tawfick was promoted from associate professor to full professor, he dedicated the book to the University Library.

Using their new method, Tawfick and his colleagues fabricated everyday items such as a pinecone, a raspberry and a squash. These are all axisymmetrical shapes, or symmetrical around a vertical axis. Non-symmetrical shapes are more difficult, but possible; for example, the researchers sculpted a kiwi bird by allowing the spherical body to expand below the surface before pulling it up just in time to create a diminutive head and minute beak.

“It is a beautiful and simple application of a reaction-diffusion process, which is found in many natural systems. The speed and energy efficiency of the growth-printing process make this process particularly attractive. On the modeling side of this collaborative project, we developed a computational tool that predicts the upward motion of the rod needed to achieve a target shape of the manufactured object,” said Philippe Geubelle, Illinois professor of aerospace engineering and co-author on the paper.

This method’s limitations are the same ones found in nature. Printing curved objects, like bananas, is theoretically possible but difficult to program mathematically, as are complex shapes “like a thorn in a rose,” Tawfick said.

“It’s hard to find a perfect cube in nature. I don’t know of any plant or organism that looks like a perfect cube. Similarly, our process cannot make a perfect cube. It’s an interesting mirror of nature,” he said.

Tawfick says the process is “simple and highly marketable” and hopes it can one day be used to create large polymer-based products like wind turbine blades. The project is funded through the U.S. Department of Energy Office of Science Basic Energy Sciences program.

“Basic energy science could lead to transformative manufacturing, meaning something with a transformative impact on our economy. This is a successful example and was made possible through collaboration here at the Beckman Institute with people from all areas of expertise,” Tawfick said.

First author and Illinois graduate student Yun Seong Kim said the project demonstrated true teamwork:

“It was really a work of true teamwork, because it required expertise in various backgrounds and we all came together to make it happen,” he said.

Coauthor Randy Ewoldt, the Alexander Rankin Professor of Mechanical Science and Engineering at Illinois, adds: “The many advances of this work resulted because of the outstanding teamwork. The Illinois culture of collaborative excellence shines bright.”

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Scientists create a type of catalog, the ‘colocatome,’ of non-cancerous cells’ influence on cancer

Even cells experience peer pressure.

Scientists have long studied the ins and outs of cancer cells to learn more about the disease, but they’re increasingly finding that noncancerous cells near the cancer cells exert a powerful influence over a tumor’s trajectory.

“Not all cells in a tumor are cancer cells — they’re not even always the most dominant cell type,” said Sylvia Plevritis, PhD, chair of Stanford Medicine’s department of biomedical data science. “There are many other cell types that support tumors.”

To better capture the whole picture of cells’ locations and interactions, Plevritis and a team of researchers have developed something that they call the “colocatome,” (pronounced co-locate-ome). Modeled after the nomenclature that describes other classes of molecules and facets of human biology (collective information about genes is called the genome; proteins, the proteome; metabolites, the metabolome, etc.) the colocatome documents the details of malignant cells on their neighbors — what those cells are and how many of them are present.

“We’ve been studying cancer cells for so long, but the picture is still incomplete,” said Gina Bouchard, PhD, instructor of biomedical data science. “Understanding tumor biology is not only about cancer cells; there’s a whole ecosystem that needs to be studied. Cancer cells need help to survive, to resist, to thrive and even sometimes to die.”

A study describing the findings was published in Nature Communications last month. Bouchard is the lead author, and Plevritis is the senior author.

Mapping influence

Cancer cells are surprisingly dependent on their surroundings. Depending on the location, type and quantity of noncancerous cells surrounding the tumor, the cells’ behavior can change, whether through faster growth, decreased susceptibility to drugs or heightened cell metabolism.

“The questions we’re asking are very simple. We want to know who the neighbors are for each cell. Who likes whom? Who doesn’t like whom? It’s all about which cells tend to be together, and which ones are rarely found together,” Bouchard said. Cells that attract each other are described as “colocalizing” while those that seem to repel each other form “anti-colocalizations.” Those colocalizations are then linked to the state of the cancer — aggressive, resistant, susceptible to drugs — and logged in the colocatome.

The team developed experimental models of lung cancer in the lab, then used artificial intelligence to analyze them, identifying noncancerous cells and how they organized within and around the tumor cells. They then compared the colocalizations with those from patient tumor biopsies. After mapping hundreds of cell configurations, they confirmed that the majority of colocalizations in the primary patient tumors are observed in the experimental models. (That overlap is key, said Bouchard. It means that the models are a valuable and accurate representation of what’s happening in someone who has lung cancer.)

Past research by Plevritis and others showed strong interactions between fibroblasts and cancer cells, but exactly how fibroblasts interact with cancer cells is unclear. In an experiment, Plevritis showed that lung cancer cells die when doused with a type of anti-tumor drug that stunts cell growth. But throw fibroblasts into the mix, and the entire landscape changes — literally. Plevritis mapped the treated tumor models and saw that post-treatment, the cancer cells and fibroblasts were generally left intact in the same amount. But they had rearranged themselves.

“That spatial reorganization appears to have given rise to drug-resistance,” said Plevritis, the William M. Hume Professor in the School of Medicine. “It was like changing the furniture in the room, then finding the exits are blocked.”

Chasing new leads

As the team continues to log spatial maps of treated and untreated tumors, they hope to unlock more configurations that help clue doctors in on why some cancers persist after treatment. Ideally, the researchers said, the colocatome could provide information that guides treatment of patient’s cancer: If a specific colocalization confers resistance to a common drug, for instance, physicians can search for another that might have a better chance of working. They also hope the colocalization maps will generate testable hypotheses to describe aspects of cancer biology that remain unclear.

As they collect more data, the team plans to employ AI to identify specific spatial motifs and create catalogs of maps that correspond to different cell states for a variety of cancers. “Then we can begin to see whether certain spatial motifs are shared between cancer types, regardless of where they originate in the body. That could reveal universal rules of tumor behavior and guide the design of more broadly effective treatments,” Plevritis said. “That’s something I’m really excited about.”

A researcher from the University of Oxford contributed to this research.

This study was funded by the National Institute of Health (grants R25CA180993, U54CA274511 and K99CA255586) and Les Fonds de Recherche du Québec.

Stanford’s Department of Biomedical Data Sciences also supported the work.

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Medical infusion bags can release microplastics

Microplastics have been found almost everywhere that scientists have looked for them. Now, according to research published in the ACS partner journal Environment & Health, these bits of plastic — from 1 to 62 micrometers long — are present in the filtered solutions used for medical intravenous (IV) infusions. The researchers estimate that thousands of plastic particles could be delivered directly to a person’s bloodstream from a single 8.4-ounce (250-milliliter) bag of infusion fluid.

In clinical settings, IV infusions are packaged in individual plastic pouches and deliver water, electrolytes, nutrients or medicine to patients. The base of these infusions is a saline solution that contains filtered water and enough salt to match the content of human blood. Research from the 1970s suggests IV fluid bags can contain solid particles, but few scientists have followed up on what those particles are made of. Liwu Zhang, Ventsislav Kolev Valev and colleagues suspected that these particles could be microplastics that, upon infusion, would enter the recipient’s bloodstream and potentially cause negative health effects. So, they set out to analyze the types and amounts of particles in commercial IV fluid bags.

The team purchased two different brands of 8.4-ounce bags of IV saline solution. After the contents of each bag dripped into separate glass containers, the liquids were filtered to catch microscopic particles. Then the researchers counted a portion of the individual plastic fragments, using that amount to estimate the total number of microplastics in the entire pouch of IV liquid and to analyze the composition of the particles.

The researchers discovered that both brands of saline contained microplastic particles made from polypropylene — the same material as the bags — which suggests that the bags shed microplastics into the solutions. And they estimated that each bag of infusion fluid could deliver about 7,500 microplastics directly into the bloodstream. This figure rises to about 25,000 particles to treat dehydration or 52,500 for abdominal surgery, which can require multiple IV bags.

The researchers recommend keeping IV infusion bags away from ultraviolet light and heat to reduce microplastic shedding, and they say that micrometer-level filtration systems could be used to remove the particles during infusion.

While there are no clinical studies to date that have assessed the health risks of microplastics exposure, the researchers say their findings will help “provide a scientific basis for formulating appropriate policies and measures to mitigate the potential threats posed by microplastics to human health.”

The authors acknowledge funding from the National Natural Science Foundation of China.

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Thousands miss NHS screenings due to admin error

Routine screening invitations were not sent because of an error dating back to 2008.

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