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GLP-1 Receptor Agonists in Solid Tumour Therapy: Exploring Their Anticancer Potential and Underlying Molecular
Daniela Lucente1, Stefania Bellino1, Anna La Salvia1
1National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, 00161 Rome, Italy.
Abstract:
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed to treat type 2 diabetes mellitus, are now being investigated as agents in oncology. Recent preclinical studies have demonstrated their antitumor activity in several solid malignancies, including pancreatic, colorectal, breast, and prostate. Importantly, GLP-1 RAs modulate key signalling pathways such as PI3K/Akt, PKA, and AMPK, and exert anti-inflammatory effects by reducing cytokine production and macrophage infiltration. Preclinical data support their antineoplastic activity in vitro and in vivo, particularly by inhibiting tumour growth and metastasis. Nevertheless, there are ongoing concerns about tumorigenic effects in certain cancer types. This review critically examines the molecular mechanisms by which GLP-1 RAs influence cancer cell proliferation, apoptosis, angiogenesis, and inflammation, and emphasizes the need for further clinical studies to determine their therapeutic relevance. It also proposes assessing GLP-1 RAs as adjuncts in the management of solid tumours.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show potential antitumor effects in preclinical cancer models by modulating key pathways. Further clinical studies are needed to confirm their therapeutic role in solid tumors.
Area of Science:
- Oncology
- Pharmacology
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established type 2 diabetes treatments.
- Emerging research explores GLP-1 RAs for their potential anticancer properties in various solid malignancies.
Purpose of the Study:
- To critically review the molecular mechanisms of GLP-1 RAs in cancer.
- To evaluate their antitumor activity and potential tumorigenic concerns.
Main Methods:
- Review of preclinical studies (in vitro and in vivo) on GLP-1 RAs in cancer.
- Analysis of molecular pathways modulated by GLP-1 RAs, including PI3K/Akt, PKA, and AMPK.
- Examination of effects on cancer cell proliferation, apoptosis, angiogenesis, and inflammation.
Main Results:
- Preclinical data indicate GLP-1 RAs possess antitumor activity, inhibiting tumor growth and metastasis.
- GLP-1 RAs modulate key signaling pathways and exert anti-inflammatory effects.
- Concerns regarding potential tumorigenic effects in specific cancer types persist.
Conclusions:
- GLP-1 RAs demonstrate preclinical antineoplastic potential through various molecular mechanisms.
- Further clinical investigation is essential to establish the therapeutic relevance of GLP-1 RAs in oncology.
- GLP-1 RAs may be considered as adjuncts in managing solid tumors.
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