New Approaches to Targeting Epigenetic Regulation in Bladder Cancer

Area of Science:

• Oncology
• Epigenetics
• Pharmacology

Background:

• Epigenetic alterations, distinct from genetic mutations, are crucial in advanced and metastatic bladder cancer.
• These alterations are reversible, presenting opportunities for novel pharmacological interventions.
• Current treatment options for advanced bladder cancer are limited, especially after failure of first- or second-line chemoimmunotherapy.

Purpose of the Study:

• To identify and collate epigenetic therapies currently in human trials for bladder cancer.
• To review epigenetic therapies in preclinical stages (in vivo and in vitro).
• To assess the potential of epigenetic inhibitors as novel treatment options for bladder cancer patients.

Main Methods:

• Searched clinical registries for ongoing epigenetic therapy trials in bladder cancer.
• Conducted a literature search for preclinical epigenetic therapies.
• Identified and categorized epigenetic inhibitors under investigation, including DNMT, HDAC, and HMT inhibitors.

Main Results:

• Twenty-five clinical trials involving epigenetic inhibitors in bladder cancer were identified, often in combination therapies.
• No Phase 3 clinical trials have been registered to date.
• DNA-methyltransferase (DNMT) inhibitors have demonstrated the most promise in early-stage investigations.

Conclusions:

• Epigenetic alterations are prevalent in bladder cancer and represent promising therapeutic targets.
• Epigenetic therapies are under active investigation, with DNMT inhibitors showing early potential.
• Further clinical research is essential to establish the efficacy of epigenetic agents in bladder cancer treatment.