Targeting histone modifiers in bladder cancer therapy - preclinical and clinical evidence.
Nat Rev Urol
; 21(8): 495-511, 2024 08.
Article
in En
| MEDLINE
| ID: mdl-38374198
ABSTRACT
Bladder cancer in the most advanced, muscle-invasive stage is lethal, and very limited therapeutic advances have been reported for decades. To date, cisplatin-based chemotherapy remains the first-line therapy for advanced bladder cancer. Late-line options have historically been limited. In the past few years, next-generation sequencing technology has enabled chromatin remodelling gene mutations to be characterized, showing that these alterations are more frequent in urothelial bladder carcinoma than in other cancer types. Histone modifiers have functional roles in tumour progression by modulating the expression of tumour suppressors and oncogenes and, therefore, have been considered as novel drug targets for cancer therapy. The roles of epigenetic reprogramming through histone modifications have been increasingly studied in bladder cancer, and the therapeutic efficacy of targeting those histone modifiers genetically or chemically is being assessed in preclinical studies. Results from preclinical studies in bladder cancer encouraged the investigation of some of these drugs in clinical trials, which yield mixed results. Further understanding of how alterations of histone modification mechanistically contribute to bladder cancer progression, drug resistance and tumour microenvironment remodelling will be required to facilitate clinical application of epigenetic drugs in bladder cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Rev Urol
Journal subject:
UROLOGIA
Year:
2024
Type:
Article
Affiliation country:
China