Understanding GDF15 and Its Role in Cancer‑Related Weight Loss
Q: What is GDF15, and why is it important in cancer‑related weight loss?
A: GDF15, or Growth Differentiation Factor 15, is a protein that the body normally produces in very small amounts. In many people with cancer, the amount of GDF15 rises sharply. When that happens, the protein sends strong appetite‑reducing signals to the brain. This loss of appetite can lead to unplanned weight loss, shrinking muscle mass, fatigue, and a drop in physical strength. These problems can make everyday life harder and may even affect how well a person can tolerate cancer treatments.
A: GDF15, or Growth Differentiation Factor 15, is a protein that the body normally produces in very small amounts. In many people with cancer, the amount of GDF15 rises sharply. When that happens, the protein sends strong appetite‑reducing signals to the brain. This loss of appetite can lead to unplanned weight loss, shrinking muscle mass, fatigue, and a drop in physical strength. These problems can make everyday life harder and may even affect how well a person can tolerate cancer treatments.
Q: How does GDF15 cause weight loss and muscle wasting?
A: GDF15 works by attaching to a receptor in the brainstem called GFRAL. Once this connection is made, signals are sent that make people feel full sooner and think less about eating. Over time, consuming less food and fewer calories force the body to break down stored fat and muscle for energy. The result is unwanted weight loss and gradual physical decline.
A: GDF15 works by attaching to a receptor in the brainstem called GFRAL. Once this connection is made, signals are sent that make people feel full sooner and think less about eating. Over time, consuming less food and fewer calories force the body to break down stored fat and muscle for energy. The result is unwanted weight loss and gradual physical decline.
Q: What evidence shows that blocking GDF15 could help reverse cancer‑related weight loss?
A: One of the most convincing examples comes from research in mice with tumors that produce high levels of GDF15. In this study, some mice were given a special antibody that blocks GDF15. Those treated mice regained almost as much weight as healthy mice, with clear improvement in both muscle and fat stores. In certain models, body weight climbed by about 15 to 20 percent compared with untreated tumor‑bearing mice. Researchers saw these positive effects repeated in several different cancer models, which strengthened the case that GDF15 is a driving force in the process.
A: One of the most convincing examples comes from research in mice with tumors that produce high levels of GDF15. In this study, some mice were given a special antibody that blocks GDF15. Those treated mice regained almost as much weight as healthy mice, with clear improvement in both muscle and fat stores. In certain models, body weight climbed by about 15 to 20 percent compared with untreated tumor‑bearing mice. Researchers saw these positive effects repeated in several different cancer models, which strengthened the case that GDF15 is a driving force in the process.
Q: What do human studies tell us so far?
A: Pfizer developed ponsegromab, a monoclonal antibody designed to neutralize GDF15’s effects. In a Phase 2 clinical trial with cancer patients who had already lost a significant amount of weight:
A: Pfizer developed ponsegromab, a monoclonal antibody designed to neutralize GDF15’s effects. In a Phase 2 clinical trial with cancer patients who had already lost a significant amount of weight:
- Those who received the highest dose gained an average of 5.6 percent more body weight than patients given a placebo over a period of 12 weeks.
- Appetite improved, and many patients reported eating more each day.
- Increases in muscle mass and physical activity were found, along with a reduction in fatigue.
- Side effects were mostly mild, such as temporary stomach upset or slight redness at the injection site, and no serious treatment‑related safety issues were seen.
The results from this trial were similar to what had been seen in animal studies: blocking GDF15 can change the course of disease‑related weight loss instead of just easing the symptoms.
Q: What other drugs are being explored to block GDF15?
A: Several research groups and companies are working on similar ideas:
A: Several research groups and companies are working on similar ideas:
- Ponsegromab (Pfizer) – currently the most advanced, with promising mid‑stage results in humans.
- Visugromab (CatalYm) – being studied both for weight loss and to help other cancer medicines work better.
- Rilogrotug (AVEO Pharmaceuticals) – in early human testing.
- FL‑501 (Flame Biosciences) – in preclinical testing, designed for strong binding and long‑lasting effects.
- GFS202A (GenFleet Therapeutics) – an antibody that targets both GDF15 and IL‑6 to address wasting and inflammation together; early clinical studies have begun in China.
- AZD8853 (AstraZeneca) – started early safety studies in people.
Other experimental approaches include small molecule drugs, engineered proteins, and direct blockers of the GFRAL receptor itself.
Q: Why is there so much interest in this target?
A: Weight loss and muscle wasting in cancer are more than just side effects of the disease. They can shorten survival, reduce energy, and make it harder for patients to receive or recover from treatments. Current options to slow or reverse this decline are limited. Research over the past decade has made it clear that GDF15 is one of the main triggers of appetite loss and wasting in cancer. By blocking it, scientists hope to restore appetite, improve body weight and muscle strength, and help people feel stronger during treatment. The early evidence, from both laboratory and clinical settings, suggests that this approach could offer a new and much‑needed tool in supportive cancer care.
A: Weight loss and muscle wasting in cancer are more than just side effects of the disease. They can shorten survival, reduce energy, and make it harder for patients to receive or recover from treatments. Current options to slow or reverse this decline are limited. Research over the past decade has made it clear that GDF15 is one of the main triggers of appetite loss and wasting in cancer. By blocking it, scientists hope to restore appetite, improve body weight and muscle strength, and help people feel stronger during treatment. The early evidence, from both laboratory and clinical settings, suggests that this approach could offer a new and much‑needed tool in supportive cancer care.