Enhancement of targeted therapy in combination with metformin on humanbreast cancer models

Background: Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor-positive (MCF-7), trastuzumab for HER2-positive (SKBR-3), and anti-ROR1 therapy against triple-negative breast cancer (MDA-MB-231). Methods: Once the expression of relevant receptors on each cell line was confirmed and appropriate drug concentrations were selected through cytotoxicity assays, the antitumor effects of both monotherapy and combination therapy were assessed in in vitro and ex ovo models. Results: The results exhibited the synergistic effects of metformin when combined with targeted therapy. This combination effectively inhibited cell growth, colony formation, migration, and invasion in vitro. Additionally, it significantly reduced tumor size and metastatic potential in an ex ovo model. Conclusions: The findings indicate that a favorable strategy to enhance the efficacy of breast cancer treatment would be to combine metformin with targeted therapies.