Targeted brain tumor treatment-current perspectives

Area of Science:

• Neuro-oncology
• Molecular Biology
• Pharmacology

Background:

• Brain tumors have a poor prognosis with limited treatment options.
• Advances in understanding tumor biology have spurred pharmaceutical development.
• Current NCI/Pharma clinical trials explore novel therapeutic strategies.

Purpose of the Study:

• To review molecular targeted agents in preclinical and clinical brain tumor studies over the past decade.
• To discuss the complexity of molecular targeting in brain tumors.
• To identify promising molecular targets and challenges in brain tumor treatment.

Main Methods:

• Literature review of preclinical and clinical studies on molecular targeted agents for brain tumors.
• Analysis of molecular targets, including ion channels, growth factor receptors, and non-coding RNAs.
• Discussion of drug delivery strategies across the blood-brain tumor barrier.

Main Results:

• Molecular targeting in brain tumors is complex, necessitating combination therapies.
• Specific targets include calcium-dependent potassium (K(Ca)) channels (e.g., gBK splice variants) and mutant epidermal growth factor receptors (EGFRvIII) in glial tumors.
• Approved drugs like Avastin and Gleevec target receptors such as VEGFR, PDGFR, and BRC-ABL/Akt.

Conclusions:

• Combination molecular therapy with cytotoxic agents is crucial for effective brain tumor treatment.
• Emerging targets include specific gene variants and microRNAs.
• Overcoming the blood-brain tumor barrier is essential for delivering novel targeted therapies, including monoclonal antibodies.