GLP1 Receptor agonists could be promising cancer fighting drugs

Some recent research has been pointing to GLP1 as a usable tool in the fight against Cancer.

Cancer research is quite a popular point for funding, so it can be easy to be cynical about whether things that are investigated are reasonable, but the growing crop of research is at least worth looking at.

The primary method of action seems to be that colon cancer cells have GLP1 receptors, which could make them easier to target with GLP1 Receptor Agonists (i.e. drugs that bind to those GLP1 receptors)

What does the research say?

Thankfully, there is much research on the possibility of GLP1 for cancer treatment. It's well known to be effective in helping with type 2 diabetes management, but increasingly cancer is also being explored.

Review/Summaries

Some of the literature includes good summaries of the state of play (why GLP1s have been linked to Cancer, and what the results show), and other general background on the facts.

While these aren't trials or top tier peer reviewed research, we think it's worth including what professionals and researchers in the field think and how they think about the link between GLP1 and cancer.

The Expanding Role of GLP-1: From Diabetes Management to Cancer Treatment

PubMed Central (PMC)Areeba Fareed

GLP-1 receptor agonist as treatment for cancer as well as diabetes: beyond blood glucose control - PubMed

Recent studies indicate that cancer is a new complication of diabetes. In Japan, cancer is the most critical cause of death in patients with type 2 diabetes. Areas covered: Unlike diabetic angiopathies, diabetes does not accelerate the onset and progression of cancer, even though diabetes and cancer …

PubMedTakashi Nomiyama

GLP1 vs. Colorectal Cancer

Some research has examined the link and the cancer-fighting effects of GLP1 on Colorectal cancers – we've listed them below.

GLP-1 Receptor Agonists and Colorectal Cancer Risk in Drug-Naive Patients With Type 2 Diabetes

This cohort study compares glucagon-like peptide 1 receptor agonists (GLP-1RAs) with 7 non–GLP-1RA antidiabetics among drug-naive patients with type 2 diabetes.

JAMA NetworkFor Authors

GLP 1 Receptor Agonists May Reduce Risk of Colorectal Cancer in Patients With High BMI and Diabetes - The ASCO Post

The ASCO Post

GLP1 vs Pancreatic Cancer

Significance of expression of glucagon-like peptide 1 receptor in pancreatic cancer

Glucagon-like peptide 1 (GLP-1) induces insulin secretion and proliferation of pancreatic β-cells, and inhibits their apoptosis through the GLP-1 receptor (GLP-1R), thus providing a foundation for using GLP-1-based therapies for the treatment of type 2 diabetes. However, doubts have emerged regarding the drug safety of these therapies. We investigated the potential role of GLP-1R in pancreatic ductal adenocarcinoma (PDAC). GLP-1R expression was semi-quantitatively evaluated by immunohistochemistry in 48 PDAC samples, and its correlations with clinicopathological features were investigated. CFPAC-1 cells were used for GLP-1R knockdown to evaluate its effects on cell proliferation, migration and invasion. GLP-1R expression was positive in 23 tumors and negative in 25 tumors. No correlations were found between GLP-1R expression status and clinicopathological characteristics. Furthermore, GLP-1R expression status did not affect the patient prognosis (P=0.74). The majority of lymph node metastases (11 of 15 samples examined; 73%) were positive for GLP-1R expression. Immunoreactivity for GLP-1R was also noted in sites of perineural and lymphovascular invasion. GLP-1R knockdown significantly reduced the proliferation, migration and invasion of CFPAC-1 cells (P<0.05). In conclusion, although GLP-1R is not an independent prognostic factor in PDAC patients, it appears to have some implications for PDAC metastatic ability.

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Another study worth reading:

Liraglutide suppresses the metastasis of PANC-1 co-cultured with pancreatic stellate cells through modulating intracellular calcium content

GLP1 vs Liver Cancer

There's one interesting study which covered the link between GLP1 and improving outcomes for liver cancer:

GLP-1 reduces the migration of hepatocellular carcinoma cells via suppression of the stress-activated protein kinase/c-Jun N-terminal kinase pathway

Prostate Cancer

Liraglutide (Victoza, Saxenda) reduces the incidence of human prostate cancer & could be used for targeting metastatic cells:

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

Objectives The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT. Materials and methods Men with mCRPC, with more than one prostate-specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with gallium68-Dota-exendin-4. We documented PET/CT PSMA-avid lesions, which were also PET/CT exendin avid, as evidence of in vivo GLP-1R expression. Results Out of the 24 men referred, three did not meet the inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Among the four men imaged, three had no exendin-avid lesions, while one had six osseous PSMA-avid lesions, three of which were also exendin avid. Conclusions We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and exendin, in one of four participants. GLP-1R expression may thus occur even in advanced-stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.

eoMark S Stein

The abstract lays everything out quite clearly (as they should):

The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, reduces human prostate cancer incidence, and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage, and whether advanced-stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove that human metastatic castrate-resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised that mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using a radiotracer bound to a GLP-1R ligand, as in exendin PET/CT.

While it's not clear that advanced stage prostate cancer would be affected, this is great news for early-stage prostate cancer.

It's not all rainbows – if GLP1s can effectively fight cancer, shortages could get worse

If GLP1 drugs are found to be effective in fighting cancer, shortages that are already making the news could become much worse.

The American Diabetes Association (ADA) has a great article on the risks and some of the strategies that can be employed to deal with this:

Special Report: Potential Strategies for Addressing GLP-1 and Dual GLP-1/GIP Receptor Agonist Shortages

Unexpected drug shortages of the long-acting glucagon-like peptide 1 (GLP-1) receptor agonists dulaglutide and semaglutide and the dual GLP-1/glucose-dependent

American Diabetes AssociationHeather P. Whitley

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