| Literature DB >> 33972682 |
Shuhei Kamada1,2, Takeshi Namekawa1,2, Kazuhiro Ikeda1, Takashi Suzuki3, Makoto Kagawa4, Hideki Takeshita4, Akihiro Yano4, Koji Okamoto5, Tomohiko Ichikawa2, Kuniko Horie-Inoue1, Satoru Kawakami4, Satoshi Inoue6,7.
Abstract
Tyrosine kinase inhibitors (TKIs) are used as targeted drugs for advanced renal cell carcinoma (RCC), although most cases eventually progress by acquiring resistance. Cancer stemness plays critical roles in tumor aggressiveness and therapeutic resistance, and dipeptidyl peptidase IV (DPP4) has been recently identified as a cancer stemness-related protein. A question arises whether DPP4 contributes to TKI efficacy in RCC. We established patient-derived RCC spheroids and showed that DPP4 expression is associated with stemness-related gene expression. TKI sunitinib resistance was rescued by DPP4 inhibition using sitagliptin or specific siRNAs in RCC cells and tumors. DPP4 expression can be inducible by retinoic acid and repressed by ALDH1A inhibition. Among type 2 diabetes patients with clinical RCC tumors, higher TKI efficacy is observed in those bearing DPP4high tumors treated with DPP4 inhibitors. This study provides new insights into TKI resistance and drug repositioning of DPP4 inhibitor as a promising strategy for advanced RCC.Entities:
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Year: 2021 PMID： 33972682 DOI： 10.1038/s41388-021-01822-5
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867