Antitumor effect of LAT1 inhibition on clear cell sarcoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16623
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kobe University
• Principal Investigator: Morishita Masayuki 神戸大学, 医学研究科, 医学研究員 (30814321)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 明細胞肉腫 / LAT1 / アポトーシス

Outline of Final Research Achievements

L-type amino acid transporter 1 (LAT1) is expressed in various malignancies and plays an important role in the uptake of essential amino acids. Meanwhile, herein, the therapeutic potential of targeting LAT1 was investigated using a human clear cell sarcoma cell line in which LAT1 is highly expressed. In the human clear cell sarcoma cell line MP-CCS-SY, JPH203, a selective LAT1 inhibitor, decreased the cellular uptake of essential amino acids, such as leucine; in combination with doxorubicin, it inhibited cell growth and promoted apoptosis. This study suggests that LAT1 could be a useful therapeutic target for clear cell sarcoma for which no standard drug therapy exists. JPH203 administration is expected to have an add-on effect on conventional anticancer drugs. This is a very useful achievement and is of great social significance for clear cell sarcoma, a rare cancer for which it is difficult to develop new treatments.

Free Research Field

骨軟部悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

明細胞肉腫においてLAT1の高発現に着目した治療はこれまでに報告がない。本研究によりLAT１の選択的阻害が明細胞肉腫の治療において新たな知見を得た。LAT1の選択的阻害が、既存のドキソルビシンなどの抗がん剤に併用することで治療効果の増強につながる可能性が示唆された。LAT1選択的阻害剤JPH203は他の癌腫での治験において人体に安全に投与可能であることが報告されており、明細胞肉腫においても従来の抗がん剤への「上乗せ効果」が期待される。新規治療開発が困難な希少癌である明細胞肉腫において非常に有用な成果であり、社会的意義も高いものである。