LAT1, a novel pharmacological target for the treatment of glioblastoma

Abstract

The L-Type Amino Acid transporter, LAT1 (SLC7A5), has a crucial role in mediating amino acid uptake into the cells, thus modulating cell growth and proliferation as well as other intracellular functions. Different studies have reported a central role of LAT1 in glioblastoma development and progression, suggesting that the modulation of its activity could be a novel therapeutic strategy. LAT1 also has an important role in the peripheral immune system, by regulating the activation status of several immune cells through modulation of the mechanistic target of rapamycin kinase. In glioblastoma (GBM), the blood-brain barrier is disrupted, which allows the recruitment of peripheral immune cells to the tumour site. These cells, together with resident microglia, contribute to cancer growth and progression. Currently, little is known about the function of LAT1 in the reprogramming of the immune component of the tumour microenvironment in the context of GBM. In this article, we review the available data on the role of LAT1 in the regulation of GBM biology, including its potential role in the tumour microenvironment, particularly in infiltrating-peripheral immune cells and resident microglial cells. In addition, we review the available data on the main pharmacological inhibitors of LAT1, aiming to evaluate their possible role as novel therapeutics for GBM.

Keywords: Amino acid; Glioblastoma; LAT1; LAT1-inhibitor JPH203; Microglia; Pharmacotherapy.