Circular RNAs: driving forces behind chemoresistance and immune evasion in bladder cancer

MJ Saadh and WS Hussein and AF Al-Hussainy and AK Bishoyi and MM Rekha and M Kundlas and V Kavitha and Z Aminov and SG Taher and M Alwan and M Jawad and H Mushtaq, NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 398, 11161-11178 (2025).

DOI: 10.1007/s00210-025-04032-y

Bladder cancer (BCa) is characterized by recurring relapses and the emergence of chemoresistance, especially against standard treatments like cisplatin and gemcitabine. Despite its significance, the molecular mechanisms underlying chemoresistance in BCa remain elusive. Recent studies have revealed that circular RNAs (circRNAs) are pivotal regulators of cancer progression and chemoresistance. Through their function as miRNA sponges and protein sequesters, circRNAs modulate the expression of key genes, ultimately driving either drug resistance or sensitivity in BCa. The complex interplay between circRNAs and chemoresistance suggests that they may represent promising therapeutic targets for overcoming treatment resistance in patients with BCa. This review aims to summarize the current understanding of circRNAs' regulatory roles in chemoresistance and provide insights into their potential as therapeutic targets, particularly in the context of cisplatin and gemcitabine resistance. Furthermore, we explore how chemoresistance can also impact tumor immune evasion, thereby affecting the tumor microenvironment. Our findings may pave the way for the advancement of innovative treatment approaches for bladder cancer.

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