For decades, cancer has claimed lives not only through its direct assault but through a secondary betrayal — the body consuming itself in a process called cachexia, which silently undermines treatment and survival in the majority of patients. Researchers at KAIST in South Korea have now traced this wasting to a precise molecular conversation in the brainstem, where a protein released by tumors instructs the body to break down its own muscle and fat. By silencing the receptor that receives this signal, their RNA-based therapy interrupted the cascade entirely — and in mouse studies, the differen
KAIST Develops RNA Therapy to Block Cancer Cachexia, Extends Survival in Mice
Cancer cachexia affects 50-80% of cancer patients, causing severe physical decline and reducing treatment effectiveness, ultimately lowering survival rates.
The body stops breaking itself down.
Mark
Why does cancer make the body eat itself, even when food is available?
Mimi
The cancer cells release a protein that travels to the brain and essentially tells it the body is starving—even though it isn't. The brain then orders the body to break down muscle and fat for energy. It's a false alarm that the cancer exploits.
Mark
And the old treatments just tried to make patients hungry again?
Mimi
Exactly. They worked on appetite, which is a symptom. But the underlying signal—the one telling the body to waste—kept running. It's like turning up the volume on a radio while the broadcast itself is still playing the wrong station.
Mark
So this new therapy silences the receiver instead?
Mimi
Yes. It prevents the brain from building the receptor that listens for the cancer's signal. Without the receiver, the message never gets through, and the body stops breaking itself down.
Mark
The mouse survival numbers—ninety percent versus twenty percent—that's enormous.
Mimi
It is. And remember, the mice were already sick when treatment started. This wasn't prevention. It was intervention in advanced disease, and it still reversed the wasting and extended life dramatically.
Mark
When might patients actually get this?
Mimi
The team is aiming for clinical trials by 2030. There's still preclinical work to do, manufacturing to set up, safety to confirm. But the path is clear now.
Il Polso
- Cancer cachexia kills quietly — affecting up to 80% of cancer patients, it causes the body to waste away even when nutrition is adequate, making chemotherapy harder to tolerate and survival less likely.
- For decades, medicine offered only appetite stimulants, treating the symptom of hunger while the underlying metabolic collapse continued unchecked.
- KAIST researchers pinpointed the source of the problem in the brainstem, where a tumor-released protein called GDF15 binds to the GFRAL receptor and commands the body to consume its own tissue.
- Their RNA therapy uses antisense oligonucleotides to silence the GFRAL gene entirely — without the receptor, the wasting signal cannot land and the cascade never begins.
- In mouse trials, 90% of treated animals survived to day 50 compared to just 20% of untreated ones, a margin that signals not incremental progress but a potential paradigm shift.
- Human clinical trials are targeted for 2030, with the therapy envisioned as an adjuvant treatment that preserves patients' strength and dignity alongside existing cancer care.
For decades, cancer has claimed lives not only through its direct assault but through a secondary betrayal — the body consuming itself in a process called cachexia, which silently undermines treatment and survival in the majority of patients. Researchers at KAIST in South Korea have now traced this wasting to a precise molecular conversation in the brainstem, where a protein released by tumors instructs the body to break down its own muscle and fat. By silencing the receptor that receives this signal, their RNA-based therapy interrupted the cascade entirely — and in mouse studies, the difference between treated and untreated animals was the difference between survival and death. The work points toward a future where cancer patients might endure their treatments with bodies intact, their strength preserved alongside their hope.
Cancer cachexia is a quiet killer. In half to four-fifths of all cancer patients, the body enters a metabolic betrayal — muscle vanishes, fat disappears, and the patient grows too weak to tolerate chemotherapy. For decades, doctors had almost nothing to offer beyond appetite stimulants, which address hunger but not the underlying collapse.
A team at KAIST, led by Professors Minho Shong and Jinkuk Kim, has identified where the problem actually lives: not in the muscles, but in the brain. Tumors release a protein called GDF15 in large quantities, which travels to the brainstem and binds to a receptor called GFRAL. Once bound, it instructs the body to stop eating and begin consuming its own tissue. The body obeys.
The team's insight was elegant: if you cannot stop the cancer from producing GDF15, you can prevent the brain from hearing it. Working through their faculty startup THOR Therapeutics, they developed an RNA-based therapy using antisense oligonucleotides to silence the gene that produces GFRAL. Without the receptor, the wasting signal cannot land.
Tested in mice with advanced cachexia, the results were striking. Treated animals recovered substantial muscle and fat mass, and their shattered metabolism began to function again. At day 50, ninety percent of treated mice survived — compared to just twenty percent in the untreated group. The difference is not marginal.
Published in Cell Reports Medicine on July 27, the research now moves toward preclinical completion and human trials targeted for 2030. If the therapy translates to patients, it could be given alongside chemotherapy to preserve the body's ability to endure treatment. Professor Shong framed the goal plainly: a patient who does not waste away can tolerate more, maintain strength, and preserve dignity. For the first time, there is a path toward stopping cachexia at its source.
Cancer cachexia is a quiet killer. Half to four-fifths of all cancer patients experience it—a metabolic betrayal where the body wastes away even as the person eats normally. Muscle vanishes. Fat disappears. The patient grows skeletal and weak. Chemotherapy becomes harder to tolerate. Treatment stops. Survival plummets. For decades, doctors have had almost nothing to offer beyond appetite stimulants, which address hunger but not the underlying collapse.
A research team at KAIST, led by Professor Minho Shong and Professor Jinkuk Kim, has identified where the problem actually lives: not in the muscles or the metabolism, but in the brain. When cancer cells spread, they release a protein called GDF15 in large quantities. This protein travels to the brainstem, where it locks onto a receptor called GFRAL. Once bound, it sends a signal that tells the body to stop eating and start consuming its own tissue—muscle first, then fat. The body obeys. It breaks itself down.
The insight is elegant: if you cannot stop the cancer from making GDF15, you can at least prevent the brain from hearing it. The team, working with their faculty startup THOR Therapeutics, developed a treatment using antisense oligonucleotides—an RNA-based therapy that silences the gene responsible for producing GFRAL. Without the receptor, the signal cannot land. The cascade of wasting never begins.
They tested this in mice already suffering from advanced cachexia. The results were striking. Treated animals showed substantial recovery of muscle and fat mass. Their metabolism, which had been shattered, began to function again. But the most telling number came at the study's endpoint, around day 50: ninety percent of the treated mice survived. In the untreated group, only twenty percent lived. The difference is not marginal. It is the difference between life and death.
What makes this work different from existing therapies is that it does not merely coax the appetite. It dismantles the mechanism driving the wasting itself. The researchers, who published their findings in Cell Reports Medicine on July 27, are now moving toward the next phase. They plan to complete preclinical work and manufacturing protocols, then begin human trials by 2030. If the therapy works in patients as it did in mice, it could become an adjuvant treatment—something given alongside chemotherapy to preserve the body's ability to endure cancer treatment and survive it.
Professor Shong noted that the team's goal is not just to extend life, but to improve it. A cancer patient who does not waste away can tolerate more aggressive treatment. They maintain strength. They preserve dignity. They have a better chance. The therapy is still years away from clinical use, but for the first time, there is a path toward stopping cachexia at its source rather than merely managing its symptoms.
Citazioni salienti
This study is significant in that it directly targeted a key receptor in the brainstem at the RNA level to suppress the root cause of cancer cachexia, rather than only temporarily boosting appetite.— Professor Minho Shong
Vuoi la storia completa?
Leggi l'originale su Mirage News ↗
Health & Medicine