evaluation of belzutifan, a repurposed drug against dmba-induced breast cancer in the balb/c mouse model

Breast cancer (bc) is one of the principal causes of cancer-related mortality globally. tumor hypoxia is a crucial feature in aggressive breast tumors, driving angiogenesis, proliferation, and treatment resistance through stimulation of hypoxia-inducible factors (hifs). belzutifan, a hif-2α inhibitor officially approved for renal carcinoma, suggests potential as a novel approach to target hypoxia-driven bc. this study aims to investigate the anti-cancer activity of belzutifan in the dmba-induced bc model in balb/c mice. a total of 40 mice were divided into five groups of 8 animals each: control, dmba-induced (disease group), belzutifan (test group), tamoxifen (standard group), and belzutifan + tamoxifen (combination group). induction of bc was done using subcutaneous administration of dmba at 15 mg/ml for 12 weeks. treatments were given for four weeks. tumor volume, body weight, food and water intake, hematological and biochemical parameters were observed. histopathology, immunohistochemistry for hif-2α, and qrt-pcr for vegfa, ccnd1, and glut1 were estimated. belzutifan significantly reduced tumor volume and restored mammary tissue structure. immunohistochemistry indicated a noticeable decrease in hif-2α, while qrt-pcr showed reduced expression of vegfa, ccnd1, and glut1 (p<0.01). combination therapy with tamoxifen further improved these effects. no significant difference was observed in biochemical and hematological parameters, except for hemoglobin levels. belzutifan confirmed a prominent anti-tumor effect in dmba-induced bc by blocking hif-2α and the molecular pathways associated with it. combination therapy showed synergistic effects with tamoxifen, proving belzutifan to be a promising candidate for adjuvant therapy in hypoxia-associated bc.