絞り込み

18438

広告

温暖化対策強化、100人分訴え (毎日新聞)

若者グループが25日夕、政府などに地球温暖化対策の強化を訴える活動を全国各地で行った。東京都千代田区の国会前では、「迫り来るタイムリミット」「石炭だめ」などのメ...

  1. 新型コロナ GoTo事業者、来月募集 「...
  2. 検証:異常気象、新たな日常 米で熱波/北...
  3. 新型コロナ 全国新たに576人 (毎日新...
  4. 新型コロナ 接種主体は市町村に ワクチン...

ニュース一覧

Colorectal cancer is the fourth cause of death from cancer worldwide mainly due to the high incidence of drug-resistance. During a screen for new actionable targets in drug-resistant tumours we recently identified p65BTK - a novel oncogenic isoform of Bruton's tyrosine kinase. Studying three different cohorts of patients here we show that p65BTK expression correlates with histotype and cancer progression. Using drug-resistant TP53-null colon cancer cells as a model we demonstrated that p65BTK silencing or chemical inhibition overcame the 5-fluorouracil resistance of CRC cell lines and patient-derived organoids and significantly reduced the growth of xenografted tumours. Mechanistically, we show that blocking p65BTK in drug-resistant cells abolished a 5-FU-elicited TGFB1 protective response and triggered E2F-dependent apoptosis. Taken together, our data demonstrated that targeting p65BTK restores the apoptotic response to chemotherapy of drug-resistant CRCs and gives a proof-of-concept for suggesting the use of BTK inhibitors in combination with 5-FU as a novel therapeutic approach in CRC patients. This article is protected by copyright. All rights reserved.
PMID: 31518438 [PubMed - as supplied by publisher]
印刷用ページを開く Endnote用テキストダウンロード