The immunoproteasome as a potential therapeutic target in cisplatin resistant small cell and non small cell lung cance

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22828
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Shoji Tetsuaki 北海道大学, 大学病院, 医員 (10881021)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 肺癌 / シスプラチン / 薬物耐性 / プロテアソーム阻害剤 / 免疫プロテアソーム阻害剤 / 臨床腫瘍学 / 分子生物学

Outline of Final Research Achievements

We established cisplatin-resistant variants from non-small cell lung cancer cell lines and small cell lung cancer cell lines. All cisplatin-resistant cells highly expressed one or both of the immunoproteasome subunit genes, PSMB8 and PSMB9, while no clear trend was observed in the expression of constitutive proteasome subunits. The cisplatin-resistant cells expressed significantly higher levels of PSMB8 and PSMB9 proteins, as well. In addition, the cisplatin-resistant variants of the H1299 and SBC3 cell lines were more sensitive to immunoproteasome inhibitors, and had significantly more proteasomal proteolytic activity than their parental counterparts. The immunoproteasome may be an effective therapeutic target in a subset of cisplatin-resistant lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant lung cancer.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

今回、作成したシスプラチン耐性肺癌細胞5株中2株において免疫プロテアソーム阻害剤が有効な治療となることが観察された。またプロテアソームによるタンパク分解活性が有効な症例を同定するためのバイオマーカーとして利用できる可能性が示された。シスプラチンをはじめとするプラチナ製剤は肺癌治療に頻用されるが数ヶ月で耐性化するため、プラチナ製剤耐性肺癌患者の数は相当数に上ると考えられるため、本研究は多くの患者の利益に資すると予想される。