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




Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Cancer

, 16:100

First Online: 07 June 2017Received: 25 January 2017Accepted: 26 May 2017DOI: 10.1186-s12943-017-0670-3

Cite this article as: Zhao, H., Wang, J., Shao, W. et al. Mol Cancer 2017 16: 100. doi:10.1186-s12943-017-0670-3

Abstract

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.

KeywordsGlioblastoma GBM PI3K mTOR Abbreviations4EBPEukaryotic initiation factor 4E–binding protein

ALTAlanine aminotransferase

ASTAspartate transaminase

BBBBlood–brain barrier

CRComplete remission

CSCCancer stem cell

DLTDose-limiting toxicity

EGFREpidermal growth factor receptor

EMTEpithelial-to-mesenchymal transition

GBMGlioblastoma multiforme

GPCRG protein-coupled receptor

GSLCGlioblastoma stem-like cell

HandNHead and neck

HCCHepatocellular carcinoma

HhHedgehog

IC50Half maximal inhibitory concentration

LSCCLung squamous cell carcinoma

MTDMaximum tolerated dose

mTORMammalian target of rapamycin

mTORCmTOR complex

NSCLCNon-small cell lung cancer

OSoverall survival

PDK-1Phosphoinositide-dependent kinase 1

PFSProgression-free survival

PHLPPPH domain and leucine rich repeat protein phosphatase

PI3KPhosphatidylinositol 3-kinase

PIP2Phosphatidylinositol 4,5-bisphosphate

PIP3Phosphatidylinositol 3,4,5-triphosphate

PRPartial remission

PTENPhosphatase and tensin homolog deleted on chromosome 10

RRResponse ratio

RTKReceptor tyrosine kinase

SmoSmoothened

TCGAThe Cancer Genome Atlas

TRAILTumor necrosis factor-related apoptosis inducing ligand

TSCTuberous sclerosis complex





Autor: Hua-fu Zhao - Jing Wang - Wei Shao - Chang-peng Wu - Zhong-ping Chen - Shing-shun Tony To - Wei-ping Li

Fuente: https://link.springer.com/







Documentos relacionados