pioglitazone + rofecoxib + temozolomide

This is a combination of three small molecule drugs—pioglitazone, rofecoxib, and temozolomide. Pioglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist primarily used as an antidiabetic agent but also investigated for its anti-tumor and antiangiogenic properties. Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor with anti-inflammatory and potential antiangiogenic effects. Temozolomide is an oral alkylating agent used in chemotherapy, particularly for brain tumors such as glioblastoma multiforme; it works by methylating DNA to induce tumor cell death. While pioglitazone and rofecoxib have been studied together in combination with other agents like trofosfamide for advanced cancers such as melanoma, soft tissue sarcoma, and angiosarcoma[1][2][3][4], there are no published studies or clinical evidence specifically describing the use of this exact triple combination (pioglitazone + rofecoxib + temozolomide). Each component has distinct mechanisms targeting tumor cells or the tumor microenvironment.