Frontiers in Anti-Cancer Drug Discovery

Volume: 5

Targeting Potassium Channels for Drug Delivery to Brain Tumors

Author(s): Nagendra S. Ningaraj and Divya Khaitan

Pp: 231-246 (16)

DOI: 10.2174/9781681080581115050010

* (Excluding Mailing and Handling)

Abstract

Brain tumors are associated with worse prognosis as the treatment options are severely limited for brain tumor patients. Although many advances in understanding the etiology and molecular biology of brain tumors have lead to breakthroughs in developing pharmaceutical strategies, the molecular targeting in brain tumors is difficult. This is because no single gene or protein can be affected by single molecular agent, requiring the use of combination molecular therapy with cytotoxic agents. Moreover, very few anticancer drugs manage to kill brain tumor cells to prolong patient survival as therapeutic levels of drug fail to cross the BTB.

In this chapter, we briefly discuss the role of ion channels, specifically calciumdependent K+ channels (BKCa) and ATP-sensitive K+ channels (KATP) channels in glioma biology and BTB permeability regulation. We have discussed our work on brain tumors, which are associated with over-expression of BKCa and KATP channels. Finally, we discuss how we targeted BKCa and KATP channels in the BTB to deliver anti-cancer drugs and imaging agents to brain tumors by breaching the BTB. We conclude that antineoplastic drug and imaging agents’ delivery can be enhanced selectively to brain tumors by targeting ion channels on BTB. This strategy has no side effects but may help in tumor regression.


Keywords: BBB: blood-brain barrier, BKCa: calcium-dependent potassium channels, BTB: blood-tumor barrier, gBK channel: glioma specific spice variant of BKCa channel gene, HBMVEC: human brain microvascular endothelial cells, KATP: ATP sensitive potassium channels, Minoxidil sulfate (MS: KATP channel agonist), NS-1619/NS 004: 1, 3-dihydro-1-5-(trifluoromethyl)-2H benzimidazol-2- one, PDGFR: platelet-derived growth factor receptor, RTKIs: receptor tyrosine kinase inhibitors, Trastuzumab (Herceptin, Her-2 inhibitor, Roche Pharmaceuticals).

Related Journals
Related Books
© 2024 Bentham Science Publishers | Privacy Policy