Pellot Ortiz Karolina I, Rechberger Julian S, Nonnenbroich Leo F, Daniels David J, Sarkaria Jann N
Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Biomedicines. 2023 Jul 2;11(7):1879. doi: 10.3390/biomedicines11071879.
Inhibition of the interaction between MDM2 and p53 has emerged as a promising strategy for combating cancer, including the treatment of glioblastoma (GBM). Numerous MDM2 inhibitors have been developed and are currently undergoing rigorous testing for their potential in GBM therapy. Encouraging results from studies conducted in cell culture and animal models suggest that MDM2 inhibitors could effectively treat a specific subset of GBM patients with wild-type or functional p53. Combination therapy with clinically established treatment modalities such as radiation and chemotherapy offers the potential to achieve a more profound therapeutic response. Furthermore, an increasing array of other molecularly targeted therapies are being explored in combination with MDM2 inhibitors to increase the effects of individual treatments. While some MDM2 inhibitors have progressed to early phase clinical trials in GBM, their efficacy, alone and in combination, is yet to be confirmed. In this article, we present an overview of MDM2 inhibitors currently under preclinical and clinical investigation, with a specific focus on the drugs being assessed in ongoing clinical trials for GBM patients.
抑制MDM2与p53之间的相互作用已成为对抗癌症（包括治疗胶质母细胞瘤，即GBM）的一种有前景的策略。众多MDM2抑制剂已被研发出来，目前正在针对其在GBM治疗中的潜力进行严格测试。在细胞培养和动物模型中进行的研究得出的令人鼓舞的结果表明，MDM2抑制剂可以有效治疗特定亚组的具有野生型或功能性p53的GBM患者。与放射治疗和化疗等临床既定治疗方式的联合治疗有可能实现更显著的治疗反应。此外，越来越多的其他分子靶向疗法正在与MDM2抑制剂联合探索，以增强个体治疗的效果。虽然一些MDM2抑制剂已进入GBM的早期临床试验阶段，但其单独使用和联合使用的疗效尚未得到证实。在本文中，我们概述了目前正在进行临床前和临床研究的MDM2抑制剂，特别关注正在为GBM患者进行的临床试验中评估的药物。
