AI Article Synopsis
- Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of just 15 months and a low 3-year survival rate of under 7%.
- Temozolomide (TMZ) is currently the only drug that has been shown to improve survival in combination with radiotherapy, while irinotecan (CPT-11) has shown moderate effectiveness in treating recurrent gliomas.
- This study investigates how well these drugs penetrate the blood-brain barrier (BBB) using an in vivo model, highlighting the role of the ABCB1 transporter, and found that TMZ, CPT-11, and its active metabolite SN-38 are all effectively transported across the BBB
Article Abstract
Glioblastoma (GBM), the most common primary brain tumor in adults, is usually rapidly fatal with median survival duration of only 15 months and a 3-year survival rate of <7 %. Temozolomide (TMZ) is the only anticancer drug that has improved survival in GBM when administered with concomitant radiotherapy. Irinotecan (CPT-11) has also shown efficacy in recurrent gliomas monotherapy with moderate response. As the efficacy of GBM treatments relies on their brain distribution through the blood-brain barrier (BBB), the aim of the present work was to study, on an in vivo model, the brain distribution of TMZ, CPT-11 and its active metabolite, SN-38. We have focussed on the role of ABCB1, the main efflux transporter at the BBB level, through pharmacokinetics studies in CF1 mdr1a(+/+) and mdr1a(-/-) mice. Our results show that TMZ, CPT-11 and SN-38 are transported by ABCB1 at the BBB level with brain/plasma ratios of 1.1, 2.1 and 2.3, respectively.
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