The findings, presented today at the American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Annual Symposium and published in Nature Medicine, demonstrated a 60.9% overall response rate (ORR) with the three-drug combination compared to 40% with the standard-of-care (SOC) treatment — chemotherapy with or without bevacizumab. In the experimental arm, 68.7% of patients had a duration of response of at least six months, compared to 34.1% of patients in the SOC arm.

Data from this multi-institutional collaboration across 28 countries supported the accelerated approval of this combination by the Food and Drug Administration (FDA) in Dec. 2024, providing an effective new first-line treatment option for patients with BRAF V600E-mutant mCRC.

“Chemotherapy has had limited efficacy as a first-line treatment in controlling the aggressive tumor growth we see in patients with this mutation,” said co-principal investigator Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology and associate vice president of Translational Integration at MD Anderson. “This new regimen highlights the importance of combining dual-targeted therapy with chemotherapy to improve patient outcomes in the first-line setting, and the durable responses are a significant development as we work to improve quality of life for these patients.”

More than 150,000 people are diagnosed with colorectal cancer each year, making it the fourth most common cancer in the U.S., according to the National Cancer Institute. BRAF mutations occur in approximately 8-12% of cases and are associated with aggressive tumor growth, low efficacy from SOC treatments and a poor prognosis, with a median overall survival less than 12 months. Previously, there were no first-line targeted therapies approved for patients with BRAF V600E-mutant mCRC.

The BREAKWATER trial was one of the first studies to utilize the FDA’s Project FrontRunner, an initiative to encourage the evaluation of therapies in earlier clinical settings for advanced cancers rather than after patients received numerous previous treatments.

The trial enrolled patients who were at least 16 years of age with previously untreated BRAF V600E-mutant mCRC. Patients were randomized equally to one of three treatment arms: SOC chemotherapy with or without bevacizumab; a dual combination of encorafenib plus cetuximab; or a triple combination of encorafenib, cetuximab and mFOLFOX6.

When researchers analyzed patient subgroups on the trial, the triple combination showed benefits across important groups, including patients with cancer spread to three or more organs and those with liver metastases.

“These results support this combination as a new first-line standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer,” Kopetz said. “It also highlights the importance of swiftly identifying molecular subtypes of colorectal cancer at diagnosis to optimize treatment strategies for our patients.”

The safety profile of this combination was consistent with the known safety profile of each respective drug. No new safety signals were identified. The most common adverse reactions included nausea, rash, fatigue, vomiting, abdominal pain, diarrhea and decreased appetite, all of which were reported in at least 25% of patients and were similar between arms.

Final calculations of progression-free survival and overall survival will be formally assessed in the next phase of the trial. Future analyses of this trial may shed light on predictive biomarkers for this combination therapy.

The study was sponsored by Pfizer Inc., and Kopetz disclosed consulting for Pfizer and receiving research funding from the company.

Researchers from Arizona State University, along with their colleagues from the National University of the Peruvian Amazon, have identified an unknown family of microbes uniquely adapted to the waterlogged, low-oxygen conditions of tropical peatlands in Peru’s northwestern Amazonian rainforest.

The new research shows these microbes have a dual role in the carbon cycle and the potential to either moderate or intensify climate change. This process can either stabilize carbon for long-term storage or release it into the atmosphere as greenhouse gases, particularly CO2 and methane.

Under stable conditions, these microbes enable peatlands to act as vast carbon reservoirs, sequestering carbon and reducing climate risks. However, environmental shifts, including drought and warming, can trigger their activity, accelerating global climate change.

And, continued human-caused disruption of the natural peatland ecosystem could release 500 million tons of carbon by the end of the century — roughly equivalent to 5% of the world’s annual fossil fuel emissions.

“The microbial universe of the Amazon peatlands is vast in space and time, has been hidden by their remote locations, and has been severely under-studied in their local and global contributions, but thanks to local partnerships, we can now visit and study these key ecosystems,” says Hinsby Cadillo Quiroz, corresponding author of the new study and a researcher with the Biodesign Swette Center for Environmental Biotechnology at ASU.

“Our work is finding incredible organisms adapted to this environment, and several of them provide unique and important services — from carbon stabilization or recycling to carbon monoxide detoxification and others.”

Cadillo-Quiroz is also a researcher with the Biodesign Center for Fundamental and Applied Microbiomics and the ASU School of Life Sciences. ASU colleague Michael J. Pavia is the lead author of the investigation.

The study, appearing in the American Society for Microbiology journal Microbiology Spectrum, emphasizes the importance of protecting tropical peatlands to stabilize one of the planet’s most significant carbon storage systems and underscores the subtle interplay between microbial life and global climate regulation.

Why peatlands are crucial for climate stability

The Amazonian peatlands are among the planet’s largest carbon vaults, storing an estimated 3.1 billion tons of carbon in their dense, saturated soils — roughly twice the carbon stored in all the world’s forests. Peatlands are critical for global carbon storage because their waterlogged conditions slow decomposition, allowing organic material to accumulate over thousands of years. These ecosystems play a crucial role in regulating greenhouse gas emissions and influencing global climate patterns.

Building on earlier research, the current study describes newly identified microbes — part of the ancient Bathyarchaeia group that forms a complex network essential to the functioning of this ecosystem. The study highlights the remarkable abilities of these microorganisms to regulate carbon cycling in peatlands. Unlike most organisms, these microbes can thrive in extreme conditions, including environments with little to no oxygen, thanks to their metabolic flexibility.

The microbes are found in the Pastaza-Marañón Foreland Basin — a vital peatland in the northwestern Amazon rainforest of Peru. Encompassing approximately 100,000 square kilometers, the basin includes vast tracts of flooded rainforest and swamps underlain by ancient peat.

These peatland microbes consume carbon monoxide — metabolizing a gas toxic to many organisms — and convert it into energy, simultaneously reducing carbon toxicity in the environment. By breaking down carbon compounds, they produce hydrogen and CO2 that other microbes use to generate methane. Their ability to survive both oxygen-rich and oxygen-poor conditions makes them well suited to Amazonian environments, where water levels and oxygen availability fluctuate throughout the year.

However, shifts in rainfall, temperature and human activities, including deforestation and mining, are disrupting this delicate balance, causing peatlands to release greenhouse gases like carbon dioxide and methane.

Climate connection

While tropical peatlands currently act as carbon sinks, absorbing more carbon than they release, they are increasingly vulnerable to climate change. Rising temperatures and altered rainfall patterns could dry out these peatlands, turning them into carbon sources.

The release of billions of tons of carbon dioxide and methane from peatlands would significantly amplify global warming. The findings emphasize the urgent need to protect tropical peatlands from human activities and climate-induced stress.

The researchers advocate for sustainable land management, including reducing deforestation, drainage and mining activities in peatlands to prevent disruptions. Further investigation of microbial communities is needed to better understand their roles in carbon and nutrient cycling.

Tracking changes in temperature, rainfall and ecosystem dynamics is also necessary to predict future impacts on peatlands.

New directions

The discovery of highly adaptable peatland microbes advances our understanding of microbial diversity and underscores the resilience of life in extreme environments. These microbes represent a key piece of the puzzle in addressing global climate challenges, showing how the tiniest organisms can have an outsized impact on Earth’s systems.

This research, supported by the National Science Foundation, marks a significant step forward in understanding the critical role of tropical peatlands and their microbial inhabitants in global carbon cycling. As climate change continues to reshape our planet, these hidden ecosystems hold lessons that may help safeguard our future.

Drug delivery systems often face two critical challenges: poor solubility and inefficient delivery within the body. Many drugs do not dissolve well, making it difficult for them to reach their intended targets. Furthermore, current delivery systems waste a significant portion of the drug during preparation — only 5-10% of the drug is successfully loaded, leading to less effective treatments.

Peptide Helpers

The research team has developed a novel solution by designing peptides — short strings of amino acids — to bind with specific drugs and create therapeutic nanoparticles. These nanoparticles are primarily composed of the drug, with a thin peptide coating that improves solubility, enhances stability in the body, and optimizes delivery to targeted areas. Remarkably, this approach achieves drug loadings of up to 98%, a dramatic improvement over traditional methods.

By using a combination of computer models and laboratory tests, new drug/peptide nanoparticles where identified. They subsequently demonstrated remarkable results in leukemia models. The nanoparticles were more effective at shrinking tumors compared to the drugs alone. Additionally, their high efficiency allows for lower doses of drugs, potentially reducing the side effects.

“Peptides, which are designed molecules made from the same building blocks as the proteins in our body, are extremely versatile,” said Co-Principal Investigator Rein Ulijn, director of the Nanoscience Initiative at CUNY ASRC and a chemistry professor at Hunter College. “We thought they could be useful in solving two big problems seen in many drugs: poor solubility and inefficient delivery. By designing a peptide that binds the drug while enhancing its solubility, we were able to create nanoparticles with very high loading.”

Customizable Technology

This innovation holds significant potential because peptides can be customized to enhance the effectiveness of various drugs. Given the vast range of possible interactions in peptide design, it may be feasible to tailor peptides for specific drugs, extending their applicability beyond cancer treatments.

“This breakthrough enables the development of better precision medicines,” said Co-Principal Investigator Daniel Heller,head of the Cancer Nanomedicine Laboratory at Memorial Sloan Kettering Cancer Center’s Molecular Pharmacology Program. “Using specially designed peptides, we can build nanomedicines that make existing drugs more effective and less toxic and even enable the development of drugs that might not be able to work without these nanoparticles.”

Naxhije “Gia” Berisha, a former CUNY Graduate Center Ph.D. student who performed much of the experimental work, highlighted the potential of the peptide approach: “We used experimental testing to identify promising peptides and computational modeling to analyze their interactions with therapeutic molecules,” she said “It’s incredible to see how simple variations in peptide sequence could match specific drugs. This suggests there may be a peptide match for every drug, potentially revolutionizing the way medicines are delivered.”

Looking Ahead

The research team is now adopting lab automation methods to further refine and accelerate the peptide-drug matching process. Their next steps include verifying the approach’s potential in a wider range of diseases. If successful, this innovation could lead to more effective treatments, reduced side effects, and significant cost savings in drug development.

In a new paper published in Advanced Materials, a team led by Professor Tobin Filleter describes how they made nanomaterials with properties that offer a conflicting combination of exceptional strength, light weight and customizability. The approach could benefit a wide range of industries, from automotive to aerospace.

“Nano-architected materials combine high performance shapes, like making a bridge out of triangles, at nanoscale sizes, which takes advantage of the ‘smaller is stronger’ effect, to achieve some of the highest strength-to-weight and stiffness-to-weight ratios, of any material,” says Peter Serles, the first author of the new paper.

“However, the standard lattice shapes and geometries used tend to have sharp intersections and corners, which leads to the problem of stress concentrations. This results in early local failure and breakage of the materials, limiting their overall potential.

“As I thought about this challenge, I realized that it is a perfect problem for machine learning to tackle.”

Nano-architected materials are made of tiny building blocks or repeating units measuring a few hundred nanometres in size — it would take more than 100 of them patterned in a row to reach the thickness of a human hair. These building blocks, which in this case are composed of carbon, are arranged in complex 3D structures called nanolattices.

To design their improved materials, Serles and Filleter worked with Professor Seunghwa Ryu and PhD student Jinwook Yeo at the Korea Advanced Institute of Science & Technology (KAIST) in Daejeon, South Korea. This partnership was initiated through the University of Toronto’s International Doctoral Clusters program, which supports doctoral training through research engagement with international collaborators.

The KAIST team employed the multi-objective Bayesian optimization machine learning algorithm. This algorithm learned from simulated geometries to predict the best possible geometries for enhancing stress distribution and improving the strength-to-weight ratio of nano-architected designs.

Serles then used a two-photon polymerization 3D printer housed in the Centre for Research and Application in Fluidic Technologies (CRAFT) to create prototypes for experimental validation. This additive manufacturing technology enables 3D printing at the micro and nano scale, creating optimized carbon nanolattices.

These optimized nanolattices more than doubled the strength of existing designs, withstanding a stress of 2.03 megapascals for every cubic metre per kilogram of its density, which is about five times higher than titanium.

“This is the first time machine learning has been applied to optimize nano-architected materials, and we were shocked by the improvements,” says Serles. “It didn’t just replicate successful geometries from the training data; it learned from what changes to the shapes worked and what didn’t, enabling it to predict entirely new lattice geometries.

“Machine learning is normally very data intensive, and it’s difficult to generate a lot of data when you’re using high-quality data from finite element analysis. But the multi-objective Bayesian optimization algorithm only needed 400 data points, whereas other algorithms might need 20,000 or more.?So, we were able to work with a much smaller but an extremely high-quality data set.”

“We hope that these new material designs will eventually lead to ultra-light weight components in aerospace applications, such as planes, helicopters and spacecraft that can reduce fuel demands during flight while maintaining safety and performance,” says Filleter. “This can ultimately help reduce the high carbon footprint of flying.”

“For example, if you were to replace components made of titanium on a plane with this material, you would be looking at fuel savings of 80 litres per year for every kilogram of material you replace,” adds Serles.

Other contributors to the project include University of Toronto professors Yu Zou, Chandra Veer Singh, Jane Howe and Charles Jia, as well as international collaborators from Karlsruhe Institute of Technology (KIT) in Germany, Massachusetts Institute of Technology (MIT) and Rice University in the United States.

“This was a multi-faceted project that brought together various elements from material science, machine learning, chemistry and mechanics to help us understand how to improve and implement this technology,” says Serles, who is now a Schmidt Science Fellow at the California Institute of Technology (Caltech).

“Our next steps will focus on further improving the scale up of these material designs to enable cost effective macroscale components,” adds Filleter.

“In addition, we will continue to explore new designs that push the material architectures to even lower density while maintaining high strength and stiffness.”

North Carolina State University researchers firmly point the finger at the South American Andes Mountains as the place where the Irish potato famine pathogen, Phtytophthora infestans, originated.

In a wide-ranging study of the genetic material found in P. infestans and other members of the Phytophthora species, the NC State researchers provide more evidence that P. infestans spread from South America to North America before wreaking havoc in Ireland in the 1840s. The pathogen still causes late-blight disease on potato and tomato plants around the world.

Much of the study’s evidence compares whole genomes of P. infestans with those of close relative pathogens — Phytophthora andina and Phytophthora betacei — which are only found in South America. The results show that these three species are very similar.

“It’s one of the largest whole-genome studies of not only P. infestans, but also the sister lineages,” said Jean Ristaino, William Neal Reynolds Distinguished Professor of Plant Pathology at North Carolina State University and corresponding author of a paper in PLOS One that describes the study. “By sequencing these genomes and accounting for evolutionary relationships and migration patterns, we show that the whole Andean region is a hot spot for speciation, or where a species splits into two or more distinct species.”

In recent decades, scientists have been split in their theories about the point of origin for P. infestans, with some hypothesizing a Mexico origin rather than a South American origin. Yet, the paper shows distinct differences between P. infestans and the two Mexican pathogen species, P. mirabilis and P. ipomoea.

“A lot of the search for resistance to this disease has focused on a wild potato species in Mexico — Solanum demissum — which was used to breed resistant potato lines that were used for the past 100 years,” Ristaino said.

“It points out the importance of looking at the center of origin where a host and pathogen have evolved together over thousands of years,” she said. “Climate change is bringing more drought to higher Andean elevations, so we could be losing some of these potatoes before we learn if they could provide resistance to late-blight disease.” Ristaino added that more research is needed to examine wild potato species from the Andes to learn more about host resistance to P. infestans.

“Our data show that there have been more migrations of the pathogen into and out of South America, and the migrations into and out of Mexico are small in comparison,” said Allison Coomber, a former NC State graduate student researcher and lead author of the paper. “We did find there was gene flow from the Andes to Mexico, and also in reverse, because there’s a big Mexican potato breeding program and potatoes have gone into the Andean region in more recent times. But in historic times it was the other way around.”

“Historic P. infestans — the samples collected from 1845-1889 — were the first to diverge from all other P. infestans populations, with modern South American and Mexican populations both showing shared ancestry derived from historic P. infestans,” Ristaino said. “Modern global trade appears to contribute to mixing together the pathogen populations in South America and Mexico.”

Amanda C. Saville, a research and laboratory specialist in Ristaino’s lab, and Ignazio Carbone, a professor of plant pathology at NC State, also co-authored the paper, along with Michael Martin and Vanessa Bieker from the Norwegian University of Science and Technology. Funding was provided by a National Science Foundation National Research Training Grant (award number 1828820), and by two USDA APHIS Plant Protection Act 7721 grants: AP21PPQ&ST000020 and AP21PPQ&ST000062.

Visual information has long been proven to affect balance—for example, strobe lights and swirling images can cause instability—but a new study published in PLOS ONE shows that sounds can also be a disruptive factor for those who have vestibular hypofunction, a vestibular system disorder resulting in impaired balance.

“People with vestibular hypofunction have difficulty in places like busy streets or train stations where the overwhelming visual information may cause them to lose balance or be anxious or dizzy,” says lead author Anat Lubetzky, associate professor of physical therapy at NYU Steinhardt School of Culture, Education, and Human Development. “Sounds are not typically considered during physical therapy, making our findings particularly relevant for future interventions.”

The researchers conducted an experiment with 69 participants divided into two groups: healthy controls and individuals with unilateral vestibular hypofunction (affecting one ear).

Participants wore a virtual reality headset that simulated the experience of being in a New York City subway. As they experienced the sights and sounds of the “subway,” they stood on a platform that measured their body movement (known as sway), while the headset recorded their head movement, two indicators of balance. Participants were provided with different subway scenarios: static or moving visuals paired with silence, white noise, or recorded subway sounds.

The results revealed that for the group with vestibular hypofunction, the moving visuals accompanied by audio (either white noise or subway sounds) resulted in the greatest amount of sway. This sway was evident by the body’s forward and backward movements, as well as head movements left to right, and head tilts upward and downward. Audio conditions did not affect the balance of the healthy individuals.

“What we’ve learned is that sound should be included as part of both the assessment of balance and intervention programs,” says Lubetzky.  “Because balance training is known to be task-specific, ideally, these should be real sounds related to patients’ typical environments and combined with salient and increasingly challenging visual cues. Portable virtual headsets are a promising tool for both assessing and treating balance problems.”

Funding for this study was provided by a grant from the National Institute on Deafness and Other Communication Disorders (R21DC018101), resources from the Icahn School of Medicine at Mount Sinai, and a grant from the National Center for Advancing Translational Science (UL1TR004419).