GLP-1 Receptor Found on Metastatic Prostate Cancer in Living Patients for the First Time | Research

The takeaway

PET/CT imaging confirmed GLP-1 receptor expression in vivo on metastatic castrate-resistant prostate cancer in one of four patients, supporting the potential for GLP-1-based cancer therapies.

First in vivo proof
For the first time, GLP-1 receptor expression was detected on living metastatic prostate cancer using PET/CT imaging — not just in cell cultures — opening the door to GLP-1-based cancer interventions

What the researchers found

One of four patients with mCRPC had three bone metastases that were positive for both PSMA (confirming prostate cancer) and gallium-68-DOTA-exendin-4 (confirming GLP-1R expression). This is the first in vivo demonstration of GLP-1R expression in metastatic prostate cancer. The patient had six PSMA-avid lesions, three of which were also exendin-avid.

Why it matters

If prostate cancer expresses GLP-1 receptors, then the millions of men taking GLP-1 drugs for diabetes or obesity might already be receiving some anti-cancer benefit. It also opens the door to using GLP-1 receptor agonists as targeted cancer therapy or for GLP-1R-targeted imaging to guide treatment decisions in prostate cancer.

The numbers in context

First study to confirm GLP-1R expression in metastatic castrate-resistant prostate cancer in human tissue specimens.

How the study worked

Pilot imaging study. Men with mCRPC and multiple PSMA-avid PET/CT lesions underwent additional PET/CT with gallium-68-DOTA-exendin-4 (a GLP-1R-targeting radiotracer). Dual-positive lesions (PSMA+ and exendin+) confirmed in vivo GLP-1R expression by metastatic prostate cancer.

Who was studied

Human metastatic castrate-resistant prostate cancer specimens

What this study cannot tell us

Extremely small sample — only 4 patients were imaged, and 17 declined participation (the study offered no therapeutic benefit). Only 1 of 4 patients showed GLP-1R expression, and not all lesions in that patient were positive, suggesting heterogeneous expression. The GLP-1R-positive rate cannot be estimated from 4 patients. The radiotracer's sensitivity may be limited.

How to read the evidence

Preliminary evidence from a very small pilot study (n=4). The finding is novel and hypothesis-generating but cannot establish the prevalence of GLP-1R expression in prostate cancer. Recruitment difficulties (17 of 24 declined) reflect the study's limitations.

When this study was published

Published in 2024, contributing to the emerging understanding of GLP-1 receptor biology in cancer.

The bigger picture

The relationship between metabolic hormones and cancer is increasingly recognized. GLP-1's presence on prostate cancer opens multiple therapeutic possibilities — from repurposing existing GLP-1 drugs as anti-cancer agents to developing GLP-1R-targeted theranostics (combined imaging and therapy). This is particularly significant given the enormous overlap between the diabetes/obesity population and prostate cancer risk population.

Questions still open

What proportion of prostate cancers express GLP-1R, and does expression level correlate with disease stage or grade?
Could GLP-1 receptor agonists be tested as adjunctive therapy in prostate cancer patients, especially given their favorable safety profile?

Common questions

Does this mean GLP-1 drugs could treat prostate cancer?

It's too early to say, but it's an encouraging signal. The fact that metastatic prostate cancer can express the GLP-1 receptor means GLP-1 drugs could potentially interact with these cancer cells. Previous lab studies showed GLP-1 drugs slowing prostate cancer cell growth. Clinical trials would be needed to test whether this translates to meaningful anti-cancer effects in patients.

If I take semaglutide for diabetes, does it protect me from prostate cancer?

Epidemiological data suggest GLP-1 RA users may have lower prostate cancer incidence, and this study shows the biological basis exists (the receptor is present on prostate cancer). However, no clinical trial has tested GLP-1 drugs specifically for prostate cancer prevention. It's a promising area of research but not yet proven.

Read the original research

The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer.

Endocrine oncology (Bristol, England), 4(1), e230015

View on PubMed ↗Publisher’s paper ↗

Citation

Stein, Mark S; Kalff, Victor; Williams, Scott G; Murphy, Declan G; Colman, Peter G; Hofman, Michael S. (2024). The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer.. Endocrine oncology (Bristol, England), 4(1), e230015. https://doi.org/10.1530/EO-23-0015