Systematic Review Finds Most Evidence Shows Ghrelin Does Not Promote Cancer Risk or Growth

The authors performed a systematic review by searching PubMed with structured queries and supplementing with reference list screening from related reviews and meta-analyses. They identified peer-reviewed original research studies — both human and animal — that investigated ghrelin, ghrelin-receptor agonists, or ghrelin genetic variants in relation to cancer risk, cancer presence, or tumor growth. Studies were categorized by whether they found positive, null, inverse, or mixed associations.

Ghrelin-based therapies are being developed to treat cancer cachexia — the severe muscle wasting and weight loss that affects many cancer patients and worsens survival. A major safety concern has been whether stimulating the ghrelin pathway could promote cancer growth. This systematic review provides reassurance that the majority of evidence points toward ghrelin being safe or even protective in cancer contexts, clearing a key hurdle for using these therapies in patients who desperately need them.

Cancer cachexia kills a significant proportion of cancer patients and has few effective treatments. Ghrelin and its analogs (like anamorelin) are among the most promising approaches for stimulating appetite and preserving muscle mass in these patients. This review addresses the elephant in the room — whether ghrelin therapy could fuel tumor growth — and largely puts that concern to rest based on available evidence. This safety signal has helped pave the way for clinical trials of ghrelin-based cachexia treatments.

The review included studies with widely varying designs, cancer types, and populations, making direct comparisons difficult. Many included studies were observational and could not establish causation. The review was limited to PubMed searches and may have missed relevant studies in other databases. Most exogenous ghrelin treatment studies were short-term, so long-term cancer effects remain unclear.