Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 17 5 2025 10 14 848 853 Fatemeh Amirzadeh-Ghasemi Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Roshanak Daie Ghazvini Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Sadegh Khodavaisy Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Seyed Jamal Hashemi Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Ali Ahmadi Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Pegah Ardi Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Mahdi Abastabar Department of Medical Mycology and Parasitology, Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Davoud Roostaei Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Zahra Rafat Department of Medical Parasitology and Mycology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran 2025 02 26 2025 05 19 Background and Objectives: The increasing incidence of antifungal-resistant Candida infections, particularly among cancer patients, emphasizes the urgency of exploring alternative therapeutic strategies. This study aimed to assess the in vitro antifungal efficacy of three anticancer agents—tamoxifen, panobinostat, and miltefosine—both individually and in combination with the antifungals fluconazole and itraconazole, against fluconazole-resistant Candida strains. Materials and Methods: A total of 21 clinical Candida isolates (C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. auris) were evaluated. Antifungal susceptibility testing was conducted following the microdilution protocol outlined by CLSI. Results: The combination of panobinostat with fluconazole exhibited full synergistic activity against C. albicans and C. tropicalis. Conversely, antagonistic effects were observed with C. parapsilosis and C. glabrata, while C. auris displayed an indifferent response. Panobinostat paired with itraconazole showed synergy exclusively against C. albicans. Similarly, miltefosine combined with itraconazole demonstrated synergism with C. albicans, but no interaction was found with fluconazole. Tamoxifen in conjunction with itraconazole revealed a synergistic response against C. albicans, antagonism with C. tropicalis, and indifference with other species. Conclusion: Certain combinations of antifungals and anticancer agents could potentiate antifungal activity against resistant Candida isolates. Therefore, precise species-level identification is vital for tailoring effective combination therapies, particularly in immunocompromised individuals. https://ijm.tums.ac.ir/index.php/ijm/article/view/5309 https://ijm.tums.ac.ir/index.php/ijm/article/download/5309/1831