Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development

Molecular Cancer

Review

Chang-peng Wu¹  Wei Shao²  Shing-shun Tony To²  Wei-ping Li³  Hua-fu Zhao⁴  Zhong-ping Chen⁵  Jing Wang⁵ 

[1] College of Clinical Medicine, Anhui Medical University, 230032, Hefei, China;Department of Neurosurgery & Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, 518035, Shenzhen, China;Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China;Department of Neurosurgery & Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, 518035, Shenzhen, China;Department of Neurosurgery & Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, 518035, Shenzhen, China;Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 510060, Guangzhou, China;Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 510060, Guangzhou, China;

关键词: Glioblastoma;    GBM;    PI3K;    mTOR;   

DOI  :  10.1186/s12943-017-0670-3

 received in 2017-01-25, accepted in 2017-05-26,  发布年份 2017

来源: Springer

【 摘 要 】

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients’ prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.

【 授权许可】

CC BY   
© The Author(s). 2017