metformin

Biguanides inhibit cytosolic mRNA translation to extend lifespan in C. elegans . Fatty acid synthesis is translationally protected by eIF3 complex subunits. pod-2 / fasn-1 inactivation amplifies biguanide-induced reductive stress and death. NADPH-generating insults require fatty acid synthesis to buffer reductive stress.

Metformin and its derivatives exert dual anticancer effects by modulating systemic insulin signaling and targeting tumor-intrinsic pathways. Nevertheless, inconsistencies between preclinical efficacy and clinical outcomes highlight the need for biomarker-guided approaches and deeper investigation into tumour-specific metabolic contects. These complementary mechanisms highlight their potential in precision BC therapy, warranting biomarker-driven studies and optimized therapeutic combinations.

P1, N=146, Recruiting, University of Alberta | Not yet recruiting --> Recruiting

P2, N=70, Completed, Cambridge University Hospitals NHS Foundation Trust | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Sep 2025

P2, N=13, Terminated, Sidney Kimmel Cancer Center at Thomas Jefferson University | Completed --> Terminated; Poor accrual

P1, N=14, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

This broad, multi-pathway modulation mirrors the phenotype produced by metformin and rapamycin, yet occurred with no detectable cytotoxicity, paralleling metformin and rapamycin with negligible cytotoxicity. Although prospective clinical outcomes are still lacking, the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate. Further research is warranted to confirm its clinical impacts, optimize dosing, and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.

This overview provides a concise synthesis of targeted therapies under investigation or already in clinical use, including monoclonal antibodies against epidermal growth factor receptor (EGFR) (e.g., cetuximab) and immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), as well as inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) or agents targeting angiogenic and intracellular signaling pathways such as VEGF and mTOR...Metformin and statins, for instance, have demonstrated anti-proliferative and pro-apoptotic effects in preclinical OSCC models. Notably, recent evidence suggests that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, may improve survival specifically in patients with PIK3CA-altered Head and Neck tumors, potentially through modulation of the COX-2/PGE2 axis. Although prospective evidence remains limited and somewhat heterogeneous, existing preclinical and observational studies suggest that these agents may improve survival and reduce treatment-related toxicity, further pointing to the relevance of molecular stratification in guiding future repurposing strategies. This article aims to map the current therapeutic landscape, highlighting both established molecular targets and emerging repositioned drugs in the management of OSCC and OPSCC.

Therapeutically, microbiota modulation via diet, metformin, and probiotics shows promise. Gut microbiota lies at the nexus of T2DM and CRC, functioning as a modifiable mediator rather than a passive bystander. Future research should prioritize longitudinal, multi-omic, and intervention-driven studies to enable personalized prevention and treatment strategies.

P1, N=45, Not yet recruiting, Duke University

P=N/A, N=50, Completed, Liaquat University of Medical & Health Sciences | Recruiting --> Completed

P1, N=16, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting