Investigational DNA topoisomerase I inhibitors for colorectal cancer: preclinical and early phase developments

Despite the success of CPT derivatives like irinotecan, topotecan and belotecan (approved drugs), drawbacks such as lactone instability have led to the development of modified compounds. Structural modifications in CPT derivatives, like derived homocamptothecins, show enhanced efficacy and reduced toxicity. Additionally, synthetic compounds like indenoisoquinolines and quinolines have emerged as potent TOP1 inhibitors. Dual inhibitors, combination therapies, integration with immunotherapy and personalized medicine further enhance treatment efficacy. Ongoing preclinical studies offer hope for improved CRC management.