Novel Biomarker for Therapeutic Target in Lung squamous cell carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Gunma University
• Principal Investigator: Rokudai Susumu 群馬大学, 大学院医学系研究科, 講師 (20392334)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: p53 / p63 / 肺がん / 扁平上皮がん

Outline of Final Research Achievements

Lung squamous cell carcinoma is difficult to treat because molecular targeted therapies are not effective. The disruption of control of the ΔNp63 gene expression, which is a diagnostic marker for squamous cell carcinoma, is one of the causes of cancer development and progression. Through comprehensive screening using a next-generation sequencer, we clarified the molecular mechanism that causes the disruption of p63 expression control related to poor prognosis, and clarified the mechanism involved in malignant transformation of cancer. In addition, in squamous cell carcinoma of the head and neck, AKT3 in cancer-related fibroblastic cells (CAF) was revealed to be associated with immunosuppression of the microenvironment of CAF, and is a potential biomarker of CAF activity and immunosuppressive microenvironment. Possibly a therapeutic target that inhibits the tumor-promoting function of CAF.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

肺扁平上皮がんの診断マーカーでもあるΔNp63の発現の増加は高頻度で認められ、90%以上の扁平上皮がんで陽性であり、p53のがん抑制機能を阻害することで、がんの発生や進行、治療への抵抗性を高めるものと考えられており、治療標的としての可能性を秘めていると考えられる。本研究では、p63遺伝子の制御に関与するがんの発生や進行の詳細な仕組みを解明し、分子標的治療の開発に繋がる可能性を検討した。p63の発現制御機構を利用した化合物スクリーニングを進めており、アカデミア創薬としての開発が期待される。