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RAGE Implicated in Worsening Breast Cancer Mortality with Age

Published

4 weeks ago

May 15, 2026

Researchers at Georgetown’s Lombardi Comprehensive Cancer Center have identified a mechanism that may help to explain why older people experience worse outcomes from breast cancer. The study in different mouse breast cancer models and in human breast cancers implicates RAGE (receptor for advanced glycation end-products), a cell surface receptor that amplifies inflammatory signaling, and which also becomes increasingly active with metastatic progression. The study findings in addition suggested that inhibiting RAGE may offer a well-tolerated adjunctive breast cancer therapy in older patients.

“Our study addresses a major gap by showing that aging dramatically increases breast cancer metastasis and that this effect depends on RAGE, a receptor on the surface of cells that fuels inflammation,” said Barry Hudson, PhD, associate professor of oncology at Georgetown Lombardi. “Most laboratory studies rely on young mice, which has limited our understanding of how aging itself alters the host environment, including immune function and chronic inflammatory states that, in turn, influence cancer behavior.” Hudson is corresponding author of the researchers’ Communications Biology published paper titled “Aging promotes a RAGE-dependent increase in breast cancer metastasis.” In their paper the authors concluded that their findings “… identify RAGE as a mechanistic link between aging and metastasis and a potential therapeutic target in older patients.” They say the findings will also be featured in the Nature portfolio special collection, Cancer and Aging.

Age is the primary risk factor for the development of adult cancers, including breast cancer, with almost half of new breast cancer diagnoses and more than half of breast cancer-specific deaths occurring in women aged 65 years and older, the authors wrote. And while advances in screening and therapy have improved survival, older women continue to have higher breast cancer-specific mortality. “Despite accumulating evidence that metastasis in murine breast cancer models increases with advancing host age, the mechanisms underlying this have not been elucidated, highlighting the need for further mechanistic studies,” the team continued.

And while breast cancer is more prevalent in older women, most cancer research in mouse models has used young, 2–3-month-old adult mice, which are about equivalent in age to 15–20-year-old humans. Timing and chance presented Hudson and colleagues with opportunities to carry out their newly reported study. During COVID, when there was reduced laboratory activity, some of the research team’s mouse colonies aged longer than originally planned. This created a rare opening to study cancer in these older animals—normally a difficult and expensive endeavor—giving the scientists the ability to directly compare how tumors behave in younger versus older mice.

RAGE is a proinflammatory molecule that is being considered as a therapeutic target in multiple aging-related diseases, including various cancers, cardiovascular and neurodegenerative diseases.

Using three different mouse models of triple-negative breast cancer (TNBC), the researchers discovered that aged mice developed substantially more lung metastases than younger mice, despite similar primary tumor growth. The team then showed that genetic deletion of RAGE in mice almost completely eliminated this age-related surge in metastasis.

Through their studies, the team demonstrated that aging increased levels of inflammatory molecules that activate RAGE. These included the proteins S100 and HMGB1, found in both primary tumors and at metastatic sites. These changes made it easier for cancer cells to invade and spread. “These findings show that aging doesn’t just increase cancer risk—it actively changes the body in ways that help tumors spread,” said Hudson. “RAGE appears to be a key mediator of these harmful age-related pathways.” In their paper the authors stated that their data “… suggest that aging promotes multiple prometastatic processes within the tumor and its microenvironment, and that RAGE is required for the induction of these inflammatory and tumor-promoting pathways in aged hosts.“

The team also analyzed breast cancer data from more than 1,000 patients and found that higher expression of AGER (the gene encoding RAGE) and related inflammatory gene signatures were associated with worse outcomes in patients, supporting the clinical relevance of their findings. They noted, “… in human breast cancers, high AGER expression, as well as enrichment for mouse tumor-derived aging- and RAGE-associated gene signatures, predicted poorer outcomes, particularly in older women …Together, these data indicate that in older individuals with breast cancer, intratumor RAGE overexpression amplifies aging-associated transcriptional programs, linking age-dependent inflammation to promote metastatic progression.”

RAGE is already being explored as a therapeutic target in several age-related diseases, highlighting its potential relevance in cancer. In prior work, the researchers had shown that the RAGE inhibitor TTP488 (azeliragon) can suppress breast cancer metastasis in preclinical models. In the current study, they also tested the drug in the lab and found that TTP488 was able to reduce tumor cell invasiveness that was induced by blood sera from aged mice.” Pharmacologic inhibition of RAGE by TTP488 (PF-04494700 or azeliragon) suppressed migration and invasion towards aged serum, further supporting the requirement of RAGE signaling for age-dependent metastasis,” the team noted.

A clinical study is underway at Lombardi evaluating TTP488 in breast cancer patients receiving chemotherapy, with a focus on safety and cognitive outcome. The drug has demonstrated a favorable safety profile in people, making it an optimal choice for further study. “TTP488 has demonstrated an excellent safety profile in Phase I/II clinical studies in older adults with Alzheimer’s disease, supporting its potential for repurposing,” the authors wrote. “Therapeutic RAGE inhibition may provide a well-tolerated means to counteract inflammaging and improve cancer outcomes in the elderly, who often face limited treatment options due to toxicity,” the investigators wrote.

“This study highlights the importance of the host environment in cancer,” Hudson added. “While cancer is often viewed as driven primarily by mutations intrinsic to tumor cells, systemic factors such as aging and inflammation play a critical role in shaping how cancers behave,” said Hudson. “Most deaths due to cancer occur because tumors spread to other organs, so understanding these influences may help identify new strategies to limit metastasis.”

The post RAGE Implicated in Worsening Breast Cancer Mortality with Age appeared first on GEN – Genetic Engineering and Biotechnology News.

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Hantavirus One-Shot mRNA Vaccine Fully Protects in Syrian Hamster Model

Published

2 hours ago

June 12, 2026

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Last month, the Andes virus outbreak on a Dutch cruise ship departing from Argentina brought a transmission context for hantavirus, that was previously unprecedented, to the forefront. The Andes virus is the only member of the hantavirus family that is capable of efficient person-to-person spread through close contact with respiratory secretions. Other hantaviruses are typically spread through contact with infected rodents, making the Andes virus a much more significant public health threat.

While at sea, the outbreak spread among passengers and crew, infecting 13 people and killing three. The cruise passengers have since returned to their home countries, 23 in total. Because a person can carry the virus for weeks before showing any symptoms, health agencies are facing a complex challenge of identifying everyone who was exposed. There are currently no vaccines or preventive treatments approved for the virus; this travel-related outbreak brought the need for vaccine development to the forefront.

Researchers at The University of Texas Medical Branch (UTMB) had previously developed and tested two mRNA vaccines against intramuscular Andes virus challenge in golden Syrian hamsters (“1-methylpseudouridine-modified or non-modified mRNA modalities encoding the envelope glycoproteins, Gn and Gc, in a single open reading frame.”)

When tested in the Syrian hamster model, both mRNA vaccines were efficacious in hamsters using a two-dose regimen. Recognizing that a fast-moving international outbreak doesn’t allow time for patients to wait weeks between shots, the team retested the vaccines to determine whether a single dose would be effective.

Now, a new report shares the finding that the vaccine provided full protection against the Andes hantavirus after a single dose.

This work is published in The Lancet in the paper, “Single-dose mRNA vaccines against Andes hantavirus.”

Alexander Bukreyev, PhD, head of the Laboratory of Viral Pathogenesis and Vaccine Development at UTMB, said that the group is working to fast-track these single-dose vaccines into human clinical trials.

The results exceeded expectations. When testing the vaccines in an animal model that mimics human disease, the scientists found that a single shot provided 100% protection against a lethal dose of the virus. Even when the researchers significantly lowered the dosage to a fraction of the original amount, the results remained definitive.

“Every vaccinated animal remained completely healthy and showed no symptoms or weight loss,” said Michelle Meyer, PhD, senior scientist in the Bukreyev Laboratory. “When we looked at the tissues from the vaccinated animals a month after infection, the virus was entirely gone. The vaccines triggered a powerful immune response, creating protective antibodies in as little as 14 days.”

Because the Andes virus can take a relatively long time to make a human severely ill, these fast-acting vaccines could serve a dual purpose, possibly functioning as an emergency tool for people who have already been exposed.

“If given quickly to high-risk contacts during an outbreak, such as the Andes virus situation on the cruise ship, the vaccines could theoretically jump-start their immune systems fast enough to intercept the virus—stopping it from replicating and preventing them from getting sick or spreading it further,” Bukreyev said.

The post Hantavirus One-Shot mRNA Vaccine Fully Protects in Syrian Hamster Model appeared first on GEN – Genetic Engineering and Biotechnology News.

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SonoThera Raises $125M to Develop Ultrasound-Mediated Genetic Medicines

Published

3 hours ago

June 12, 2026

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Biotechnology company SonoThera has raised $125 million in an oversubscribed Series B financing round. The financing was led by Vida Ventures, with participation from ARK Invest, CureDuchenne Ventures, Leaps by Bayer, Otsuka Pharmaceutical, SymBiosis, UCB Ventures SA, Vivo Capital, and existing investors ARCH Venture Partners, Alexandria Venture Investments, Duquesne Family Office, Illumina Ventures, Johnson & Johnson Innovation – JJDC, Medical Excellence Capital, RA Capital, and Vertex Ventures HC.

SonoThera will use the funds to advance its lead programs in Duchenne muscular dystrophy (DMD) and autosomal dominant polycystic kidney disease (ADPKD) in the clinic. The funds will also support efforts to expand its pipeline of targeted redosable genetic medicines across multiple organ systems and scale its proprietary platform technologies for safe, targeted therapy delivery.

The company’s platform combines a proprietary ultrasound-mediated delivery technology dubbed RIPPLE, with a payload engineering platform dubbed PORE. The platforms are designed to support the development of DNA and RNA therapeutics, gene editing, and gene silencing approaches. SonoThera is using its tech to develop genetic medicines that it claims will address key limitations of conventional gene therapies including delivery challenges, payload size constraints, immune responses, safety events, and difficulties with redosing.

As Kenneth Greenberd, PhD, SonoThera’s co-founder and CEO, stated “we founded SonoThera to take a fundamentally different approach, with a platform designed to broaden the therapeutic possibilities of the field. We believe our technology has the potential to expand the range of diseases addressable by genetic medicines while enabling more precise, durable, safer, and repeatable therapies for patients.”

SonoThera has already demonstrated the targeted delivery and expression capabilities of its platform across multiple tissues, including skeletal muscle, heart, liver, kidney, adipose, and brain. It has also shown that it can deliver large payloads such as full-length dystrophin for DMD and RNA-based payloads for gene silencing applications in preclinical studies.

The company expects to initiate its first clinical trial in DMD in 2027.

Commenting on the financing, Rajul Jain, MD, managing director at Vida Ventures, said “we believe SonoThera, with its RIPPLE delivery and PORE payload engineering technologies, has the potential to unlock opportunities in diseases with significant unmet need that have been previously inaccessible to other genetic medicine approaches.”

In connection with the financing, Jain and Rakhshita Dhar, MS, vice president & head of Healthcare Venture Investments at Leaps by Bayer, have joined SonoThera’s Board of Directors.

The post SonoThera Raises $125M to Develop Ultrasound-Mediated Genetic Medicines appeared first on GEN – Genetic Engineering and Biotechnology News.

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STAT+: Up and down the ladder: The latest comings and goings

Hired someone new and exciting? Promoted a rising star? Finally solved that hard-to-fill spot? Share the news with us, and we’ll share it with others. That’s right. Send us your changes, and we’ll find a home for them. Don’t be shy. Everyone wants to know who is coming and going.

And here is our regular feature in which we highlight a different person each week. This time around, we note that AstronauTx hired Michelle Mellion as chief medical officer. Previously, she held the same role at PepGen and EveryONE Medicines.

But all work and no play can make for a dull chief medical officer.

Continue to STAT+ to read the full story…

Published

6 hours ago

June 12, 2026

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