Oral Ghrelin Agonist Reduces Cancer Wasting in Mice by Boosting Appetite and Preserving Muscle

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.

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.

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.

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.