Exploring market-approved azoles as potential breast cancer therapeutics targeting the VEGFR-2 biotarget

Abstract

Abstract Cancer is a complicated, deadly disease, ranking as the second leading cause of death globally. The World Health Organization (WHO) reported nearly 20 million new cases of cancer in 2022, and this burden is anticipated to be doubled by 2035. Breast cancer is one of the most prevalent malignancies and the leading cause of mortality among women globally. As per the GLOBOCAN 2022 database, breast cancer represented 25% of cancer incidence and around 20% of cancer deaths among women in the Middle East and North Africa region (MENA). Although there have been significant developments in surgical, radiotherapeutic, and immunological strategies, chemotherapy remains the major therapeutic approach for cancer treatment. Therefore, there is an urgent necessity for the evolution of innovative and effective therapies against cancer. Vascular endothelial growth factor receptor-2 (VEGFR-2) is an essential regulator of angiogenesis, significantly influencing cancer proliferation and is considered among the most promising targets for cancer treatment. Notably, azole-based derivatives appeared as a promising pharmacophore in combating various diseases and possessed a significant potential to emerge as effective therapeutic options for cancer treatment. Pacing up the drug discovery process, drug repurposing has emerged as a prospective approach owing to its efficiency in saving both time and cost for proven drug kinetics and safety profile. Herein, molecular modelling simulations-coupled biological testing were applied to screen and investigate the potential inhibitory activity of some market-approved azoles against VEGFR-2 biotarget. The anti-fungal azole itraconazole emerged as a promising agent targeting VEGFR-2 to halt angiogenesis and tumour growth, warranting further preclinical and clinical investigations.