BACKGROUND/AIM: Amino acids are among the most important nutrients for supplying energy and building protein blocks in cancers. L-type amino acid transporter (LAT) 1 is known to play a critical role in cancer growth. We have completed the first-in-human phase I study using the LAT1-specific inhibitor JPH203. PATIENTS AND METHODS: We evaluated plasma free amino acids (PFAAs), body mass index (BMI), and efficacy of JPH203 in patients enrolled in the phase I study. RESULTS: LAT1-substrate PFAAs and branched chain amino acids (BCAAs) were higher in patients with biliary tract cancer (BTC) than in those with other cancers. High inhibition of uptake of LAT1-substrate PFAAs was associated with survival. BMI of more than the median was associated with disease control and survival. BCAAs tended to be associated with BMI. CONCLUSION: BCAAs and BMI are useful predictors of the efficacy of JPH203, which shows promising activity against BTC. Copyright
BACKGROUND/AIM: Amino acids are among the most important nutrients for supplying energy and building protein blocks in cancers. L-type amino acid transporter (LAT) 1 is known to play a critical role in cancer growth. We have completed the first-in-human phase I study using the LAT1-specific inhibitor JPH203. PATIENTS AND METHODS: We evaluated plasma free amino acids (PFAAs), body mass index (BMI), and efficacy of JPH203 in patients enrolled in the phase I study. RESULTS:LAT1-substrate PFAAs and branched chain amino acids (BCAAs) were higher in patients with biliary tract cancer (BTC) than in those with other cancers. High inhibition of uptake of LAT1-substrate PFAAs was associated with survival. BMI of more than the median was associated with disease control and survival. BCAAs tended to be associated with BMI. CONCLUSION:BCAAs and BMI are useful predictors of the efficacy of JPH203, which shows promising activity against BTC. Copyright
Authors: Yann Cormerais; Pierre André Massard; Milica Vucetic; Sandy Giuliano; Eric Tambutté; Jerome Durivault; Valérie Vial; Hitoshi Endou; Michael F Wempe; Scott K Parks; Jacques Pouyssegur Journal: J Biol Chem Date: 2018-01-11 Impact factor: 5.157