Monday, February 9, 2015

FL118 agent shows efficacy as personalized, targeted therapy for certain cancer tumors




A team led by Fengzhi Li, PhD, and Xinjiang Wang, PhD, of Roswell Park Cancer Institute (RPCI) has reported new findings regarding therapeutic targets of the novel anticancer agent FL118. Previous studies from these researchers have showed that FL118 induces cancer cell death, or apoptosis, by inhibiting expression of multiple cell-survival proteins (survivin, Mcl-1, XIAP or cIAP2). Study results published in the peer-reviewed American Association for Cancer Research journal Cancer Research  showed that FL118 can also activate   the p53 tumor-suppressor pathway in cancer cells, encouraging cell senescence,    or aging. In both processes, FL118 demonstrates potent antitumor efficacy,   suggesting additional applications as a personalized, targeted therapy for certain cancer tumors.

In a study of preclinical models of colorectal cancer, the researchers identified an underlying mechanism for the activation of p53 by FL118. The agent activates the p53 tumor-suppressor protein largely independent of ataxia telangiectasia mutated (ATM)-dependent DNA damage-mediated p53 activation. ATM-dependent activation of p53 is usually induced by many — if not all  types of DNA-damage drugs, including camptothecin compounds such as irinotecan and topotecan,  leading  the authors  to  conclude  that  FL118's mechanisms of action are distinct among camptothecin analogues.


"While FL118 is an analogue of irinotecan and topotecan, two FDA-approved cancer drugs that are also based on the naturally occurring compound camptothecin, our findings add further evidence that FL118 has novel mechanisms of action that may make it especially potent against solid tumors and especially effective as a well-tolerated, targeted therapy," said Dr. Li, an Associate Professor of Oncology in the Department of Pharmacology and Therapeutics.





















FL118 agent shows efficacy as personalized, targeted therapy for certain cancer tumors

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