The evolution of antifungal therapy: Traditional agents, current challenges and future perspectives
Cássia Milena de Souza, Bárbara Tavares Bezerra, Daniel Agreda Mellon, Haroldo César de Oliveira
Abstract
• Over 6.5 million people face invasive fungal infections annually, with high mortality rates due to limited drug options, toxicity, costs, and increasing resistance. • Current antifungal drugs primarily target the fungal cell membrane, DNA synthesis, or cell wall, limiting treatment efficacy and promoting resistance. • New antifungal agents are in clinical trial stages with new mechanisms of action and/or improvements in the activity of the former. • Drug repurposing, nanotechnology, antifungal peptides, combination therapies, and immunotherapies are tools with great potential to provide new antifungal alternatives. • The urgent development of safer, affordable antifungals with diverse targets is essential to save millions of lives annually. Fungal infections kill more than 3 million people every year. This high number reflects the significant challenges that treating these diseases worldwide presents. The current arsenal of antifungal drugs is limited and often accompanied by high toxicity to patients, elevated treatment costs, increased frequency of resistance rates, and the emergence of naturally resistant species. These treatment challenges highlight the urgency of developing new antifungal therapies, which could positively impact millions of lives each year globally. Our review offers an overview of the antifungal drugs currently available for treatment, presents the status of new antifungal drugs under clinical study, and explores ahead to future candidates that aim to help address this important global health issue.