Genetic biomarkers of drug response for small-molecule therapeutics targeting the RTK/Ras/PI3K, p53 or Rb pathway in glioblastoma. (April 2016)

• Record Type: Journal Article
• Authors: Venkatesan, Subramanian; Lamfers, Martine LM; Dirven, Clemens MF; Leenstra, Sieger
• Is Part Of: CNS oncology. Volume 5:Number 2(2016)
• Page Start: 77
• Page End: 90
• Publication Date: 2016-04
• Subjects: brain tumor -- genetic biomarkers -- glioblastoma -- personalized medicine -- resistance -- small-molecule kinase inhibitors; Central nervous system -- Tumors -- Periodicals; 616.99481
• DOI: 10.2217/cns-2015-0005
• Languages: English
• ISSNs: 2045-0907

Abstract

Glioblastoma is the most deadly and frequently occurring primary malignant tumor of the central nervous system. Genomic studies have shown that mutated oncogenes and tumor suppressor genes in glioblastoma mainly occur in three pathways: the RTK/Ras/PI3K signaling, the p53 and the Rb pathways. In this review, we summarize the modulatory effects of genetic aberrations in these three pathways to drugs targeting these specific pathways. We also provide an overview of the preclinical efforts made to identify genetic biomarkers of response and resistance. Knowledge of biomarkers will finally promote patient stratification in clinical trials, a prerequisite for trial design in the era of precision medicine.