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
