Broad-Bayer collaboration leads to drug candidate for a hard-to-treat type of lung cancer

Broad Communications Scientists in the Broad-Bayer oncology alliance have developed a drug candidate, sevabertinib, that could be a new lung cancer treatment.
Illustration Credit: Agnieszka Grosso

An alliance of scientists at the Broad Institute and Bayer Pharmaceuticals have developed a drug candidate, sevabertinib, that could be a new treatment for a group of lung cancer patients who have few options today.

In a new study published in Cancer Discovery, the team described their efforts to develop sevabertinib. They tested the compound in various lung cancer models and showed its potential to treat non-small cell lung cancers that harbor certain mutations in the ERBB2 gene, which encodes the HER2 protein. These mutations occur in 2 to 4 percent of patients with non-small cell lung cancer, or roughly 40,000 to 50,000 people diagnosed globally each year. These patients tend to be women, including those who are younger, have never smoked, and have a poor prognosis. 

The study also reported data from two participants in Bayer’s phase 1/2 clinical trial of the compound. Based on these findings and other data from this ongoing clinical trial, the drug candidate is currently under Priority Review at the FDA, an expedited review of therapies that treat serious conditions. If approved, it would be the first FDA-approved cancer drug based on Broad discoveries, and the first new medicine from the Broad-Bayer oncology research alliance. 

New antivirals could help prevent cold sores by changing cell structures

Pin1 inhibitors suppress HSV-1 replication by inhibiting viral protein synthesis and preventing nucleocapsid egress from the nucleus.
Illustration Credit: Takemasa Sakaguchi/Hiroshima University

A class of antivirals called Pin1 inhibitors could reduce or stop outbreaks of herpes simplex virus 1 (HSV-1), the common infection behind oral herpes, according to new research published in Antiviral Research.

HSV-1 causes sores around the mouth, commonly called cold sores or fever blisters. Most people are infected with HSV-1 in childhood, and between 50% and 90% of people worldwide have HSV-1. After the initial infection, HSV-1 remains in the body and can reactivate throughout a person’s life. While HSV-1 infections are usually mild, they can be serious and even deadly for people with suppressed immune systems. Finding new, more effective antivirals for this common illness is essential. 

Researchers focused on an enzyme called peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, or Pin1, that regulates protein stability, function, and cellular structure. When this enzyme is dysregulated, it can play a role in a variety of conditions, including obesity, cancer, heart failure, and more. Viruses, such as cytomegalovirus (CMV) and SARS-CoV-2, are known to affect Pin1, and Pin1 inhibitors have been developed to reduce the impact of these viruses. 

When Machines Learn to Feel

Changes in heart rate can provide information about physical and emotional well-being. 
Photo Credit: © RUB, Kramer

In addition to linguistic prompts, large language models can also understand, interpret, and adapt their responses to heart frequency data. Dr. Morris Gellisch, previously of Ruhr University Bochum, Germany, and now at University of Zurich, Switzerland, and Boris Burr from Ruhr University Bochum verified this in an experiment. They developed a technical interface through which the physiological data can be transmitted to the language model in real time. The AI can also account for subtle physiological signals such as changes in heart activity. This opens new doors for use in medical and care applications. The work was published in the technical journal Frontiers in Digital Health.

Archaeologists uncover 5,000-year-old ceremonial site in Jordan

Dolmen found at Murayghat in Jordan.
Photo Credit: Susanne Kerner, University of Copenhagen

A research team led by the University of Copenhagen has uncovered a remarkable Early Bronze Age ritual landscape at Murayghat in Jordan. The discovery can shed new light on how ancient communities responded to social and environmental change.

How did ancient cultures respond to crises and the collapse of the established social order? The 5,000-year-old Early Bronze Age site of Murayghat in Jordan, which has been extensively excavated by archaeologists from the University of Copenhagen, may hold an answer.

Murayghat emerged after the decline of the so-called Chalcolithic culture (ca. 4500–3500 BCE), a period known for its domestic settlements, rich symbolic traditions, copper artifacts, and small cultic shrines.  

When healing turns harmful: adrenal support cells tied to cancer origin

Image Credit: Scientific Frontline / AI generated

A new study from Karolinska Institutet, shows that support cells in the adrenal gland can regenerate hormone-producing tissue after birth. The same cells may also act as a starting point for adrenal tumors, offering new insights into cancer development and potential treatment strategies.

“We found that these glial-like cells not only help maintain healthy tissue but, in some paragangliomas, also carry the same tumor-initiating genetic event,” explains Susanne Schlisio, group leader at the Department of Oncology-Pathology and last author of the study. 

“In tumors with germline VHL mutations, subsets of these support cells showed loss of chromosome 3p, the ‘second hit’ leading to VHL inactivation. This suggests they may be the origin of certain tumors,” says Dr. Michael Mints, docent at the same department and co-corresponding author of the study.

In a surprising discovery, scientists find tiny loops in the genomes of dividing cells

MIT experiments have revealed the existence of “microcompartments,” shown in yellow, within the 3D structure of the genome. These compartments are formed by tiny loops that may play a role in gene regulation.
Illustration Credit: Ed Banigan, edited by MIT News
(CC BY-NC-ND 4.0)

Before cells can divide, they first need to replicate all of their chromosomes, so that each of the daughter cells can receive a full set of genetic material. Until now, scientists had believed that as division occurs, the genome loses the distinctive 3D internal structure that it typically forms.

Once division is complete, it was thought, the genome gradually regains that complex, globular structure, which plays an essential role in controlling which genes are turned on in a given cell.

However, a new study from MIT shows that in fact, this picture is not fully accurate. Using a higher-resolution genome mapping technique, the research team discovered that small 3D loops connecting regulatory elements and genes persist in the genome during cell division, or mitosis.

“This study really helps to clarify how we should think about mitosis. In the past, mitosis was thought of as a blank slate, with no transcription and no structure related to gene activity. And we now know that that’s not quite the case,” says Anders Sejr Hansen, an associate professor of biological engineering at MIT. “What we see is that there’s always structure. It never goes away.”

New study finds large fluctuations in sea level occurred throughout the last ice age, a significant shift in understanding of past climate

Photo Credit: Michael Chen

Large changes in global sea level, fueled by fluctuations in ice sheet growth and decay, occurred throughout the last ice age, rather than just toward the end of that period, a study published this week in the journal Science has found.

The findings represent a significant change in researchers’ understanding of how the Pleistocene – the geological period from about 2.6 million to 11,700 years ago and commonly known as the last ice age – developed, said Peter Clark Link is external, a paleoclimatologist at Oregon State University and the study’s lead author.

“This is a paradigm shift in our understanding of the history of the ice age,” said Clark, a university distinguished professor in OSU’s College of Earth, Ocean, and Atmospheric Sciences.

During the last ice age, Earth experienced cycles of dramatic shifts in global sea level caused by the formation and melting of large ice sheets over northern areas of North America and Eurasia. These changes are recorded in the shell remains of microscopic marine organisms called foraminifera, which are found in ocean sediment and collected by drilling cores, giving scientists an important record of past climate history.

Muscle wasting reversed in patients with rheumatoid arthritis

Photo Credit: Roger Vaughan

Patients with rheumatoid arthritis increased their leg muscle volume when treated with an anti-rheumatic drug, offering new hope for improved muscle health.

Publishing in the prestigious journal, The Lancet Rheumatology, the team from Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust describe how 15 patients were given Tofacitinib, a Janus kinase (JAK) inhibitor used to treat RA, as part of an experimental medicine study. After 6 months their leg muscles increased in size, particularly in the thigh.  

Sarcopenia is a progressive, age-related musculoskeletal disease characterized by the loss of muscle mass, strength, and physical performance, increasing the risk of falls, fractures, physical disability, and mortality. Currently there are no medicines approved to reverse this muscle-wasting disease. It is commonly seen in patients with rheumatoid arthritis where chronic inflammation contributes to the loss of muscle mass and strength.

Hotter does mean wetter

How rising temperatures will affect rainfall in Japan.
Illustration Credit: KyotoU / Takemi lab

Around the world, we are already witnessing the detrimental effects of climate change, which we know will only become more severe. Extreme weather events such as heavy rainfall, tropical cyclones, and heat waves are projected to intensify, and this will negatively impact both human society and natural ecosystems.

Assessing how climate change affects extreme weather is important not only from a scientific point of view, but also from a practical perspective. It is critical that we start adapting to climate change and mitigating the effects of potential disasters.

This situation has motivated a team of researchers at Kyoto University to investigate how climate change -- in particular, rising temperatures -- affects precipitation in Japan. The team has focused on heavy rainfall patterns and what kind of atmospheric conditions influence their characteristics.

The Many FACES of Lipid Research

Subcellular lipid distributions (magenta) in mitochondria (green) revealed using FACES and super-resolution structure illuminated microscopy.
Image Credit: William Moore

Lipids are fatty molecules that play critical roles in cell function, including membrane structure, energy storage and nutrient absorption. Most lipids are made in a cell organelle called the endoplasmic reticulum, but specific lipid types are shuttled around to different parts of the cell depending on their purpose. Each organelle serves a specific role in a cell and has its own unique mixture of lipids called a lipidome.

Scientists have long wanted to get a closer look at the movement of lipids around a cell, but because organelles are so close together – often only tens of nanometers apart – it’s tough to visualize with traditional light microscopy, which only has resolutions up to 250 nanometers.

Now researchers at the University of California San Diego have unveiled a new technology with the power to see cells in unprecedented detail. The tool, called fluorogen-activating coincidence encounter sensing (FACES), was developed in Associate Professor of Biochemistry & Molecular Biophysics Itay Budin’s lab. This work appears in Nature Chemical Biology.