Obstacles to Brain Tumor Therapy: Key ABC Transporters

• Published in: International journal of molecular sciences 2017-11, Vol.18 (12), p.2544
• Main Authors: Wijaya, Juwina, Fukuda, Yu, Schuetz, John D
• Format: Article
• Language: English
• Subjects: ABC transporter; Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; ATP-Binding Cassette Transporters - chemistry; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Blood-brain barrier; Blood-Brain Barrier - metabolism; blood–tumor barrier; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain tumors; Cancer; Cancer therapies; Chemotherapy; CNS; Endothelial cells; glioma; Glioma - drug therapy; Glioma - metabolism; Humans; medulloblastoma; Metastases; Metastasis; Parenchyma; Review; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18122544

The delivery of cancer chemotherapy to treat brain tumors remains a challenge, in part, because of the inherent biological barrier, the blood-brain barrier. While its presence and role as a protector of the normal brain parenchyma has been acknowledged for decades, it is only recently that the important transporter components, expressed in the tightly knit capillary endothelial cells, have been deciphered. These transporters are ATP-binding cassette (ABC) transporters and, so far, the major clinically important ones that functionally contribute to the blood-brain barrier are ABCG2 and ABCB1. A further limitation to cancer therapy of brain tumors or brain metastases is the blood-tumor barrier, where tumors erect a barrier of transporters that further impede drug entry. The expression and regulation of these two transporters at these barriers, as well as tumor derived alteration in expression and/or mutation, are likely obstacles to effective therapy.