Table 3 Outlook

EGFR

EGFR inhibitors or antibody appear inactive, partly due to the existence of BBB

Target on EGFR amplification and EGFRvIII

PI3K/AKT/mTOR

Most of the drugs experience poorly tolerance, and the regulation of this pathway is far too complex

combine PI3K/SKT/mTOR inhibitors with other drugs

MET

There is still no effective kind of drugs

Combination of c-MET inhibitor and PI3K inhibitors due to their cooperation to drug resistance

FGFR

Population of patients that could gain benefit from this target is extraordinarily small

BRAF

Mutations of this target are rare

BRAFv600E in GBM needs to be further studied

NTRK

The incidence of NTRK gene fusion seems to be very low in glioblastoma

NTRK fusion as a therapeutic target is active and molecular heterogeneity screening in the diagnosis of GBM is significant

pRB

Regulation of cell cycle and apoptosis is complex

P53

Effort on promoting the refolding of mutant proteins into wild-type conformations meets failure

Inhibitors of MDM2/4 and Weel kinase

TERT

Though TERT mutation is commonly identified in GBM, it has not yet become the main pharmacological target for tumor therapy

Novel inhibitors need to be developed

proteasome

TGF-β

The function of TGF β protein family is complex and the regulatory pathways are widely crossed

Combine TMA and TGF inhibitors

PD-1

Combine PD-1 and other immunotherapy target

LAG-3

there are few trials about LAG-3 inhibitors or antibodies involved in GBM therapy

CTLA-4

CTLA-4 inhibitors combined with TMZ, anti-PD-1 or other drugs appear promising

IDO1

Enzymatic and non-enzymatic activity of IDO

CD73 and CD39

In tumor microenvironment, both CD73 and CD39 participate in regulation of ATP-adenosine axis

CD27-CD70

Combination of CD27 agonist and CD70 inhibitor

CD276

Un-defined isoforms and intracellular domain with unknown ligand

CD276 is correlated with angiogenesis

CD47

Polymorphism of SIRPα, ligand of CD47

Anti-CD47 promotes phagocytosis of glioma