Nearly 74% of studies found no link or an inverse link between ghrelin and cancer, suggesting ghrelin-based cachexia treatments are likely safe for cancer patients.
73.8% of studies: no cancer riskNearly three-quarters of 61 reviewed studies found ghrelin had no effect on or was inversely associated with cancer risk and growth
What the researchers found
This systematic review examined 61 in vivo studies on ghrelin, ghrelin-receptor agonists, and ghrelin genetic variants in relation to cancer. Nearly three-quarters (73.8%) of studies found either no statistically significant association or an inverse association between ghrelin and cancer risk, presence, or growth.
Notably, all 11 studies that specifically tested treatment with exogenous ghrelin or ghrelin-receptor agonists reported null or inverse cancer associations. Only 16.7% of all reviewed studies found a positive association, and 10% reported mixed results. Cancer patients tended to have lower serum ghrelin levels than controls for some cancer types, though not all.
Why it matters
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.
The numbers in context
61 studies reviewed · 73.8% null or inverse association · 16.7% positive association · 10% mixed · all 11 exogenous treatment studies showed no cancer-promoting effect
How the study worked
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.
Who was studied
61 in vivo studies (human and animal) examining ghrelin in relation to cancer
What this study cannot tell us
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.
How to read the evidence
This is rated Moderate evidence because it is a systematic review — a strong study design — but the underlying studies are heterogeneous in design, cancer types, and populations. The review was not a meta-analysis with pooled statistical results, and many included studies were observational rather than controlled trials.
When this study was published
Published in 2016, this review is now 10 years old. More recent studies and clinical trials of ghrelin analogs like anamorelin have since provided additional safety data, generally consistent with these findings.
The bigger picture
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.
Questions still open
- Could long-term ghrelin treatment over months or years affect cancer risk differently than short-term studies suggest?
- Why do some cancer types show lower ghrelin levels while others do not, and what does this mean for targeted treatment?
- Would ghrelin-receptor agonists like anamorelin show the same safety profile in large-scale cancer cachexia trials?
Common questions
Does ghrelin cause cancer or make it worse?
Why is ghrelin being studied for cancer patients if there are cancer concerns?
Read the original research
Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.
Endocrine-related cancer, 23(9), R393-409
Citation
Sever, Sakine; White, Donna L; Garcia, José M. (2016). Is there an effect of ghrelin/ghrelin analogs on cancer? A systematic review.. Endocrine-related cancer, 23(9), R393-409. https://doi.org/10.1530/ERC-16-0130