PT  - JOURNAL ARTICLE
AU  - Mihaila, Romeo Gabriel
TI  - A minireview on NHE1 inhibitors. A rediscovered hope in oncohematology
DP  - 2015 Dec 3
TA  - Biomedical papers
PG  - 519--526
VI  - 159
IP  - 4
AID - 10.5507/bp.2015.060
IS  - 12138118
AB  - Background: Na<sup>+</sup>/H<sup>+</sup> exchanger-1 (NHE-1) is involved in pH regulation and is up-regulated in different malignancies. Activation of NHE-1 is one way for allowing cells to avoid intracellular acidification and protect them against apoptosis. Inhibitors of NHE-1 are able to decrease intracellular pH and induce apoptosis. Some statins can also act by partial inhibition of NHE-1. This review presents progress in understanding the mechanisms of action of these inhibitors, connections with certain genetic mutations and acquired treatment resistance, as well as new patents on them.
Methods: A MEDLINE search for original and review articles using key terms, Na<sup>+</sup>/H<sup>+</sup> exchanger, leukemia, cariporide, and amiloride. Recent patents with NHE-1 inhibitors published by United States Patent and Trademark Office are also presented.
Results and Conclusions: Sorafenib is used for the treatment of acute myeloid leukemia patients carrying internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD) mutation. 5-(N, N-hexamethylene)-amiloride can increase the suppression of FLT3 signaling by sorafenib. NHE-1 inhibitors are able to increase the sensitivity of chronic myeloid leukemia cells to tyrosine kinase inhibitors, including through the inhibition of P-glycoprotein. NHE-1 inhibitors are promising adjuvant drugs for overcoming acquired resistance to treatment in various malignant hemopathies.