An oral drug that mimics ghrelin's effects increased food intake, body weight, muscle mass, and bone density in mice with cancer cachexia, even without reducing the inflammatory signals driving the wasting.
Muscle + bone preservedHM01 protected both skeletal muscle mass and bone mineral density in tumor-bearing mice — two of the most devastating losses in cancer cachexia
What the researchers found
An oral ghrelin receptor agonist called HM01 significantly reduced cancer-related wasting (cachexia) in mice with colon tumors. Treated mice had increased food intake, body weight, fat mass, muscle mass, and bone mineral density, while energy expenditure decreased. Notably, these benefits occurred even though HM01 did not reduce the inflammatory cytokines (IL-6 and MIC-1) or muscle degradation markers (MuRF-1 and MAFbx) that drive cachexia. This suggests HM01 works by boosting caloric intake and reducing energy burning rather than blocking the inflammatory wasting pathways directly.
The study also mapped the timeline of cachexia progression: the inflammatory cytokine MIC-1 rose first, followed by IL-6, and muscle degradation markers increased last.
Why it matters
Cancer cachexia — the severe muscle and weight loss that accompanies many cancers — affects up to 80% of advanced cancer patients and directly contributes to death. There are currently no approved drugs that effectively treat it. The fact that an oral ghrelin agonist could preserve muscle and bone mass in this model, without needing to block the underlying inflammatory cascade, opens up a practical treatment strategy that could work alongside anti-cancer therapies.
How the study worked
Researchers inoculated mice with colon-26 tumor cells to induce cancer cachexia, then treated them orally with HM01, a non-peptide ghrelin receptor agonist. They tracked body weight, body composition (fat and lean mass via DEXA-like scanning), bone mineral density, food intake, and energy expenditure over the course of tumor development. They also measured inflammatory cytokines (IL-6 and MIC-1) and muscle degradation markers (MuRF-1 and MAFbx) to understand the mechanism.
Who was studied
BALB/c mice bearing colon-26 tumors (cancer cachexia model)
What this study cannot tell us
This is a mouse study using a single tumor model (colon-26), so results may not translate to humans or other cancer types. The C26 model produces cachexia without severe anorexia, which may not represent all forms of cancer cachexia. HM01 is a non-peptide small molecule rather than a peptide itself, though it acts on the ghrelin peptide pathway. No long-term survival data were reported.
How to read the evidence
Rated Low-Moderate because this is a preclinical mouse study using a single tumor model. While the results are mechanistically informative and the study was well-designed, animal results frequently do not translate to humans.
When this study was published
Published in 2017, this study represents early-stage preclinical work on oral ghrelin agonists for cancer cachexia. The ghrelin pathway remains an active area of cachexia research.
The bigger picture
Ghrelin-based therapies have been explored for cancer cachexia for over a decade, but most candidates have been injectable peptides. An oral ghrelin agonist like HM01 would be far more practical for cancer patients who are already dealing with treatment burden. This study adds to the evidence that targeting the ghrelin pathway can meaningfully combat wasting, even when the underlying inflammatory drive of cachexia remains active.
Questions still open
- Would HM01 show similar benefits in cancer cachexia models with severe anorexia, not just the mild appetite loss seen in C26 tumors?
- Does preserving body weight and muscle through ghrelin agonism improve survival in tumor-bearing animals?
- Could combining a ghrelin agonist with an anti-inflammatory agent produce even greater anti-cachexia effects?
Common questions
What is cancer cachexia and why is it so dangerous?
How does a ghrelin agonist fight cancer wasting if it doesn't stop the inflammation?
Read the original research
Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.
International journal of molecular sciences, 18(5)
Citation
Villars, Fabienne O; Pietra, Claudio; Giuliano, Claudio; Lutz, Thomas A; Riediger, Thomas. (2017). Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.. International journal of molecular sciences, 18(5). https://doi.org/10.3390/ijms18050986