Combination of approved chemotherapeutics and natural products for topoisomerase II targeting: efficacy and safety in cancer therapy

Abstract Cancer is characterized by abnormal cell growth and remains a leading global cause of death despite advances in conventional therapies. Limitations such as lack of selectivity, cytotoxic side effects, and multidrug resistance underscore the need for potent anticancer agents. Topoisomerase II (TOP2) has emerged as a pivotal target for anticancer drugs, categorized as poisons and catalytic inhibitors. While clinically used TOP2-based drugs predominantly act as poisons, concerns regarding their cytotoxicity and DNA-damaging potential persist. In response to these challenges, exploring natural bioactive compounds (NBCs), including small molecules from Chinese herbs, as sources of novel anticancer agents has become a focal point in pharmaceutical research. Recognizing that NBCs alone may not satisfy as anticancer agents, this review aims to comprehensively analyze the current published studies, specifically focusing on the combined applications of TOP2-inhibiting approved chemotherapeutics and natural products. The review explores this approach's potential synergies and challenges, emphasizing the importance of developing effective and targeted anticancer strategies.