Camptothecin analog FL118 can overcome treatment resistance, outperform approved therapies


The latest research from the team that discovered the novel anticancer agent FL118 highlights distinctive characteristics of this small-molecule compound and provides insights into its ability to overcome the persistent problem of treatment resistance. In findings reported in Molecular Cancer, Fengzhi Li, PhD, of Roswell Park Cancer Institute (RPCI), and colleagues provide new evidence that FL118 may be more effective than two structurally similar injectable drugs and, additionally, may be effective as an oral agent.

Like the FDA-approved cancer therapies irinotecan and topotecan, FL118 is an analog of camptothecin, a natural compound used in traditional Chinese medicine. But unlike those drugs, Dr. Li and co-authors report, FL118 activates the tumor-suppressor protein p53 independent of ATM, or the ataxia-telangiectasia mutated protein kinase. That distinct mechanism of action means that FL118 can effectively bypass treatment resistance resulting from overexpression of the drug-efflux pump protein ABCG2, a limitation associated with both irinotecan and topotecan.