LAT1 (L-type amino acid transporter 1: SLC7A5) is one of system L amino acid transporters, which transport large neutral amino acids including essential amino acids (Leu, Ile, Phe, Met Val). LAT1 is highly expressed in various cancer cells including pancreatic ductal adeno carcinoma (PDAC). In various cancers, it has also been reported that patients with high LAT1 expression in tumor lesions have a poorer prognosis than those with low LAT1 expression in tumor lesion in various cancers. However, anticancer drug targeting LAT1 have not yet been established.
We have developed a non-competitive inhibitor against LAT1. This compound reduced the viability in various tumor cells and suppressed the growth of various xenograft tumor in mice. Furthermore, it prolonged the prognosis of genetically engineered mice with PDAC. Therefore, we planned to apply for clinical use of this compound as an anticancer drug.
After conducting various safety tests, a detailed protocol was decided. There were various hurdles for academia to conduct a FIH trial as investigator-initiated clinical trial. Fortunately, with various support, we were able to start the clinical trials in 2019.In this session, we would like to introduce our experience, including various challenges to the investigator-initiated clinical trial.