Pharmacotherapy for adults with tumors of the central nervous system

Abstract

Tumors of the adult central nervous system are among the most common and most chemoresistant neoplasms. Malignant tumors of the brain and spinal cord collectively account for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Novel pharmacological approaches to nervous system tumors are urgently needed. This review presents the current approaches and challenges to successful pharmacotherapy of adults with malignant tumors of the central nervous system and discusses novel approaches aimed at overcoming these challenges.

Fig. 1

Fractional incidence of subtypes of nervous system gliomas (Central Brain Tumor Registry of the United States, 2007).

Fig. 2

EGFR signaling through the PI3K/Akt pathway. Erlotinib and gelfitinib interfere with autophosphorylation of EGFR. In tumors that exhibit upregulation of IGFR, signaling of that receptor through Ras/Raf can bypass the block and generate sufficient activated PI3K to signal through Akt; these tumors are therefore resistant to erlotinib and gelfitinib. Adjunctive treatment with farnesyl transferase inhibitors or nelfinavir can overcome this resistance.

Fig. 3

c-MET signaling pathways are both independent of and overlapping with EGFR signaling.