MGMT expression is a critical mechanism for resistance to CRT in solid tumors, including glioblastoma, and decreasing MGMT expression would provide significant therapeutic benefit.6, 12, 36, 37 Various strategies to deplete MGMT have been previously reported and include the use of a dose-dense temozolomide regimen, pseudo-substrates of MGMT such as O6-Benzylguanine and O6-4-bromothenyl guanine, quinolone derivatives, S-adenosylmethionine and S-adenosylhomocysteine, and delivery of targeted short interfering RNA (siRNA) delivered in liposomes. The gene discussed is MGMT; the disease is glioblastoma.