Inhibition of IRAK1/4 enhances the antitumor effect of lenvatinib in anaplastic thyroid cancer cells

Yoshifumi Kawamura, Ken Saijo, Hiroo Imai, Chikashi Ishioka

Research output: Contribution to journalArticlepeer-review

Abstract

Anaplastic thyroid cancer (ATC) is an extremely aggressive tumor associated with poor prognosis due to a lack of efficient therapies. In Japan, lenvatinib is the only drug approved for patients with ATC; however, its efficacy is limited. Therefore, novel therapeutic strategies are urgently required for patients with ATC. The present study aimed to identify compounds that enhance the antiproliferative effects of lenvatinib in ATC cells using a compound library. IRAK1/4 Inhibitor I was identified as a candidate compound. Combined treatment with lenvatinib and IRAK1/4 Inhibitor I showed synergistic antiproliferative effects via the induction of cell cycle arrest at G2/M phase in the ATC cell lines 8305C, HTC/C3, ACT-1, and 8505C. Furthermore, IRAK1/4 Inhibitor I enhanced the inhibition of ERK phosphorylation by lenvatinib in 8305C, HTC/C3, and 8505C cells. In an HTC/C3 xenograft mouse model, tumor volume was lower in the combined IRAK1/4 Inhibitor I and lenvatinib group compared with that in the vehicle control, IRAK1/4 Inhibitor I, and lenvatinib groups. IRAK1/4 Inhibitor I was identified as a promising compound that enhances the antiproliferative and antitumor effects of lenvatinib in ATC.

Original languageEnglish
Pages (from-to)4711-4721
Number of pages11
JournalCancer science
Volume112
Issue number11
DOIs
Publication statusPublished - 2021 Nov

Keywords

  • IL-1
  • IRAK
  • anaplastic thyroid carcinoma
  • angiogenesis
  • lenvatinib

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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