GLP-1 Drugs Show Promise Beyond Weight Loss: Potential Applications in Cancer Treatment

GLP-1 Agonists: A Versatile Class of Drugs

GLP-1 receptor agonists, known for their powerful weight loss benefits, are emerging as potential game-changers in the field of oncology. Deborah Phippard, chief scientific officer at Precision for Medicine, describes these drugs as "some of the most complicated" she has seen in her career, citing their wide-ranging effects on multiple biological pathways.

Popular drugs like Novo Nordisk's Ozempic and Wegovy, and Eli Lilly's Mounjaro and Zepbound, initially developed for diabetes and obesity treatment, are now being investigated for their potential role in cancer care. The recent U.S. approval of Wegovy for metabolic dysfunction-associated steatohepatitis (MASH) further underscores the versatility of these medications.

Potential Mechanisms in Cancer Treatment

The potential benefits of GLP-1 agonists in cancer treatment are multifaceted. Phippard explains that obesity and diabetes are well-documented risk factors for various cancers, particularly pancreatic, endometrial, ovarian, and colorectal cancers. By controlling obesity, GLP-1 drugs could theoretically reduce cancer incidence.

Beyond weight loss, these drugs may impact cancer formation and progression through immunological pathways. Phippard notes that GLP-1 agonists can demonstrably change the function of specific T cells, NK cells, macrophages, and dendritic cells. They also affect key signaling pathways such as MAP kinase, NF-kappa B, and VEGF, all of which are relevant to cancer biology.

Early research suggests that GLP-1 drugs might help overcome chemotherapy resistance and potentially enhance the effects of cancer immunotherapies like Merck & Co.'s Keytruda or Bristol Myers Squibb's Opdivo. However, Phippard cautions that the exact mechanisms are not yet fully understood, and more research is needed.

Challenges and Future Directions

While the potential of GLP-1 drugs in cancer treatment is promising, several challenges remain. Physicians are currently cautious about using these drugs in oncology, particularly for pancreatic cancer patients or those with pre-existing gastrointestinal issues. Long-term use of GLP-1 agonists is associated with muscle loss, which could be problematic for cancer patients.

The widespread use of GLP-1 drugs – with nearly 12% of Americans having taken them – presents both opportunities and challenges for cancer research. Phippard emphasizes the need for careful consideration of GLP-1 use in clinical trial design to ensure accurate data interpretation.

While standalone use of GLP-1 agonists for cancer treatment is not imminent, their potential as combination therapies alongside chemotherapy or immunotherapy is generating excitement in the oncology community. Phippard anticipates significant developments in this area over the next five to ten years, with major cancer meetings likely to feature research on GLP-1 drugs in oncology.

As the pharmaceutical industry continues to explore the full potential of GLP-1 agonists, their impact on cancer treatment could represent a significant advancement in patient care, showcasing the unexpected benefits that can arise from versatile drug classes.