bortezomib + temozolomide + radiation therapy

Bortezomib + temozolomide + radiation therapy is a combination regimen investigated primarily for the treatment of newly diagnosed or recurrent glioblastoma multiforme (GBM). Bortezomib is a small molecule proteasome inhibitor that disrupts protein degradation, leading to inhibition of cell growth and induction of apoptosis in tumor cells. Temozolomide is an oral alkylating agent that damages DNA, resulting in tumor cell death. Radiation therapy uses high-energy x-rays to kill cancer cells and shrink tumors. The rationale for this combination is that bortezomib can deplete O6-methylguanine-DNA methyltransferase (MGMT), thereby sensitizing tumor cells to temozolomide by overcoming resistance mechanisms, while also inhibiting autophagy-induced survival signals. This multi-modal approach aims to enhance cytotoxicity against GBM compared with standard chemoradiation[1][2][4][5].