Mechanism of resistance to cabozantinib in renal cell carcinoma based on expression of influx and efflux transporters

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16043
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Okayama University
• Principal Investigator: Matsumoto Jun 岡山大学, 医歯薬学域, 助教 (60709012)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: カボザンチニブ / 腎細胞がん / OATP2A1 / MATE1

Outline of Final Research Achievements

Renal cell carcinoma (RCC) is the most frequently observed cancer in the kidney. The clinical outcome for patients with RCC has improved with recent advances in cancer therapy; however, the overall prognosis remains unsatisfactory. Cabozantinib (CAB) has been approved for the treatment of advanced RCC. CAB is an effective agent against RCC; however, most RCC patients who received prior treatment with a tyrosine kinase inhibitor show resistance to CAB. The aim of this study was to elucidate the mechanism of resistance to CAB in RCC based on expression of influx and efflux transporters, such as OATP2A1 and MATE1. In this study, both of the transporters have a minor role in transporting of CAB, but these expression levels were significantly correlated the prognosis of RCC patients. The findings of the present study may facilitate better understanding of the importance of OATP2A1 and MATE1 and may have implications for future prognostication and treatment planning for patients with RCC.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究で、OATP2A1およびMATE1の発現が腎癌患者の予後に影響を及ぼすことが初めて明らかとなった。一方で、これらのトランスポーターがCABの輸送を担う可能性は低いことが示唆された。今後はOATP2A1やMATE1以外のトランスポーターによるCABの輸送を解析する必要があるが、両トランスポーターを含めて、CABのみならず他の分子標的薬の感受性や患者予後に関わるトランスポーターを複数特定することで、腎癌患者に対する治療の個別適正化が推進されることが期待される。