metformin

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). There are no objective responses among TP53 mutated ECs and among NSMP (no specific molecular profile) tumors with RB1 or CCNE1 alterations; CTNNB1 mutations correlate with clinical benefit. Pharmacokinetic analyses demonstrate that administration of letrozole and abemaciclib with metformin result in a more than 3-fold increase in metformin exposure.

P1, N=16, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

Furthermore, genetic disruption of the interaction between metformin and PRMT6 attenuates the inhibitory effect of metformin on breast cancer growth. Together, this work identifies a previously unrecognized mechanism for metformin to inhibit breast cancer growth.

Here, the angiogenesis behavior of human MDA-MB-231 cells was monitored after modulation of autophagy response in the presence of free 3-methyladenine (3-MA), metformin (Met), or drug-loaded exosomes (3-MA@Exos and Met@Exos)...These data indicate that autophagy modulation can alter the angiogenesis and metastatic behavior of human BC cells in vitro and in vivo. Exos are valid bio-shuttles for the delivery of autophagy modulators in CSC-targeted therapies.

Innovative treatments are being explored, including combination therapies such as metformin with 4SC-202, which show promise in reducing tumor cell migration and enhancing chemotherapy sensitivity. Additionally, nanoengineered formulations of cisplatin aim to improve drug delivery specificity and minimize systemic toxicity, offering a more patient-friendly approach...Addressing these areas is crucial for advancing prevention, enabling early diagnosis, and improving survival and quality of life for patients with OCSCC. This work supports ongoing progress in oral cancer research and clinical care.

Following CPCM@HA endocytosis, the loaded Cu and metformin (Met) were selectively released in response to the acidic tumor microenvironment, inducing mitochondrial dysfunction and triggering apoptosis via excessive ROS and NO generation...Consequently, tumor proliferation and metastasis were significantly suppressed, resulting in robust anti-tumor immunity. Collectively, this work not only proposed a promising strategy for potentiating immunotherapy through dual T cell activation and metabolic modulation, but also provided new insights to circumvent the limitations of immunotherapy in cancer treatment.

P3, N=274, Completed, Novo Nordisk A/S | Active, not recruiting --> Completed

P3, N=90, Completed, Ain Shams University | Recruiting --> Completed

The therapeutic role of metformin to treat brain tumors remains debated. Our findings show that drug delivery is essential, as in vivo, tumor growth decreases at concentrations below 10 nanomolar. We propose that sustained CNS metformin levels may improve tmCLIC1 inhibition, providing a basis for optimizing interactions with metformin or related compounds to enhance therapeutic efficacy.

These findings suggest that baicalein may represent a promising, non-toxic therapeutic option for endometrial cancer, particularly when used in combination with metformin. Further investigation is warranted to assess the clinical relevance of this strategy.

Risk can be attenuated through progestin-based therapy (levonorgestrel-releasing intrauterine system or continuous oral regimens), structured weight management, and metabolic adjuncts in selected phenotypes (e.g., metformin for insulin resistance; incretin-based anti-obesity agents as emerging options)...Overall, a practical precision-prevention approach-combining progestins with durable weight control and metabolic optimization under guideline-concordant surveillance-appears feasible in routine gynecologic care. Future research should establish causal effects, durability, and optimal sequencing/combination of interventions in trials with endometrial endpoints.

The review highlights metformin as the most promising anti-diabetic agent for OC management, showing anti-tumor effects through mTOR inhibition. Novel therapeutics, such as GLP-1 agonists, particularly semaglutide, may be helpful but require further clinical validation. Understanding the shared molecular pathways enables the development of integrated therapeutic strategies that target both conditions simultaneously, and it supports effective screening programs, personalized prevention strategies, and optimized multidisciplinary management approaches for this high-risk patient population.