Targeting Potassium Channels for Drug Delivery to Brain Tumors
Pp. 231-246 (16)
Nagendra S. Ningaraj and Divya Khaitan
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.
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).
Department of Molecular Oncology Research, Scintilla Bio-MARC Pvt. Ltd., Near Bangalore University, Bangalore 560056, KA, India.