Journal
MOLECULAR CANCER THERAPEUTICS
Volume 8, Issue 2, Pages 407-414Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-08-0854
Keywords
-
Categories
Funding
- Mayo Foundation
- National Cancer Institute [CA108961, CA127716]
- Brain Tumor Funders Consortium
Ask authors/readers for more resources
Resistance to temozolomide and radiotherapy is a major problem for patients with glioblastoma but may be overcome using the poly (AD P-ribose) polymerase inhibitor ABT-888. Using two primary glioblastoma xenografts, the efficacy of ABT-888 combined with radiotherapy and/or temozolomide was evaluated. Treatment with ABT-888 combined with temozolomide resulted in significant survival prolongation (GBM12: 55.1%, P = 0.005; GBM22: 54.4%, P = 0.043). ABT-888 had no effect with radiotherapy alone but significantly enhanced survival in GBM12 when combined with concurrent radiotherapy/temozolomide. With multicycle therapy, ABT-888 further extended the survival benefit of temozolomide in the inherently sensitive GBM12 and GBM22 xenograft lines. However, after in vivo selection for temozolomide resistance, the derivative GBM12TMZ and GBM22TMZ lines were no longer sensitized by ABT-888 in combination with temozolomide, and a similar lack of efficacy was observed in two other temozolomide-resistant tumor lines. Thus, the sensitizing effects of ABT-888 were limited to tumor lines that have not been previously exposed to temozolomide, and these results suggest that patients with newly diagnosed glioblastoma may be more likely to respond to combined temozolomide/poly(ADP-ribose) polymerase inhibitor therapy than patients with recurrent disease. [Mol Cancer Ther 2009;8(2):407-14]
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available