Mechanism-based design of agents that selectively target drug-resistant glioma

• Published in: Science (American Association for the Advancement of Science) Vol. 377; no. 6605; pp. 502 - 511
• Main Authors: Lin, Kingson, Gueble, Susan E., Sundaram, Ranjini K., Huseman, Eric D., Bindra, Ranjit S., Herzon, Seth B.
• Format: Journal Article
• Language: English
• Published: United States The American Association for the Advancement of Science 29.07.2022
• Subjects: Antineoplastic Agents, Alkylating - chemistry; Antineoplastic Agents, Alkylating - pharmacology; Antineoplastic Agents, Alkylating - therapeutic use; Brain; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain tumors; Cancer; Cell Line, Tumor; Chemotherapy; Dacarbazine - pharmacology; Dacarbazine - therapeutic use; Deoxyribonucleic acid; DNA; DNA Methylation - genetics; DNA Modification Methylases - genetics; DNA repair; DNA Repair - genetics; DNA Repair Enzymes - genetics; Drug Design; Drug development; Drug resistance; Drug Resistance, Neoplasm - genetics; Glial cells; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioma; Humans; Lesions; Repair; Spinal cord; Temozolomide; Temozolomide - pharmacology; Temozolomide - therapeutic use; Tumor Suppressor Proteins - genetics; Tumors

Approximately half of glioblastoma and more than two-thirds of grade II and III glioma tumors lack the DNA repair protein O 6 -methylguanine methyl transferase (MGMT). MGMT-deficient tumors respond initially to the DNA methylation agent temozolomide (TMZ) but frequently acquire resistance through lo...