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Therapeutic Strategies for MMAE-Resistant Bladder Cancer Through DPP4 Inhibition

GSE306410 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2025/08/30 Platform GPL24676
Summary
Monomethyl auristatin E (MMAE) is used as the cytotoxic payload for enfortumab vedotin (EV) in the treatment of locally advanced and metastatic bladder cancer (BC). However, the development of resistance to MMAE in BC is a therapeutic problem. To explore the mechanism of resistance to MMAE in BC, we established MMAE-resistant BC cells (MR-BCs). RNA sequencing analysis showed that the expression of dipeptidyl peptidase 4 (DPP4, also called CD26) increased significantly in MR-BCs compared with parental BC cells. Knock down of DPP4 expression using small interfering RNA inhibited the viability of MR-BCs. In addition, the DPP4 inhibitor sitagliptin suppressed the proliferation, migration, and invasion of BC cells, and cotreatment with MMAE effectively induced cell apoptosis, arrested cells in the G2M phase of the cell cycle, increased reactive oxygen species production by inhibiting the AKT pathway, and significantly inhibited the in vivo growth of MMAE-resistant cells. This study provides insights into the use of DPP4 inhibitors as a treatment strategy for MMAE-resistant BC.
Published in
Therapeutic strategies for MMAE-resistant bladder cancer through DPP4 inhibition
Li G, Tatarano S, Yoshino H et al. · Molecular oncology 2026 · PMID 41422479 · doi:10.1002/1878-0261.70187
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Direct links to NCBI, no account and no request form: the whole study as GSE306410_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1310591 and SRA study SRP612366. Searching any of these in the dataset finder brings you back here.

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