ADPB Sensitivity in Breast Cancer is Correlated with LAT1 Expression: An in vitro Study of a Novel Theranostic Candidate.

Introduction: The most common cancer in women worldwide is breast cancer. Current systemic chemotherapies do not target specific cells, which makes them toxic to normal cells. The L-type amino acid transporter 1 (LAT1) is overexpressed in a lot of cancers, also in breast cancer. Few ligand such as JPH203 (KYT-0353), a known tyrosine analogue that specifically blocks LAT1, but have limitation. It has led to efforts to create next-generation LAT1 inhibitors or prodrugs with better qualities for target therapy or diagnostic. Purpose: We investigated a new agent (S)-2-amino-4-(3,5-dichlorophenyl) butanoic acid (ADPB) as a new LAT1 inhibitor in three breast cancer cell lines: MCF-7 luminal A, HCC1954 HER2+, and MDA-MB-231 triple-negative. We hypothesized that the levels of LAT1 expression would influence the efficacy of ADPB. This could lead to a treatment that is more targeted and less harmful. Methods: We used RT-qPCR to determine the LAT1 mRNA expression in each cell line and MTT for find IC Results: ADPB diminished the viability of cells in all cell lines, and the effect was dose-dependent. MDA-MB-231 was the most sensitive cell line (IC Conclusion: In this exploratory in vitro study, ADPB predominantly induces cytostatic effects, with cellular sensitivity associated with LAT1 expression in breast cancer cell line.