Low-Toxicity Anticancer Agent Proves Effective Against a Variety of Cancers

Researchers have discovered that the small chemical molecule FL118, a new formulation of a promising anticancer agent, is even more effective in controlling two kinds of cancer than an older version of the compound proved to be six months earlier. Further findings also suggest that the agent may successfully treat other solid tumors as well.

In their earlier research, a team led by Fengzhi Li, PhD, associate professor of oncology in Roswell Park Cancer Institute’s (RPCI; Buffalo, NY, USA) department of pharmacology and therapeutics, demonstrated that FL118 eliminated human colon and head-and-neck tumors in animal models without relapse but was limited in that it could be delivered only by intraperitoneal (IP) administration. This new study, to be published in the April 8, 2013, issue of the American Journal of Translational Research, compares the earlier formulation of the agent to a new version that can also be administered intravenously, adapting it to a much wider potential clinical application.

Comparing the antitumor effectiveness and therapeutic index, or relative toxicity, of FL118 in its new intravenous (IV) formulation with the earlier form, the researchers found that maximum tolerated dose increased three- to seven-fold, depending on dosing regimen. While the original formulation contained Tween 80 or polysorbate 80, a solvent typically included in drug formulations, the agent in its new composition is free of Tween 80, resulting in significantly lower toxicity.

FL118 is a targeted therapy that selectively inhibits the expression of four major cancer-survival gene products: survivin, XIAP, Mcl-1, and/or cIAP2. Whereas both studies assessed the compound’s effectiveness against models of head-and-neck and colon tumors, other research from Dr. Li’s lab suggests that mesothelioma, ovarian, and pancreatic cancers, and potentially other solid tumors, may also be good targets for treatment with FL118.

“This work represents a significant move forward,” noted Dr. Li, senior author on the study. “We’re targeting four of the most resilient and pervasive cancer survival mechanisms, and because the findings from preclinical testing have been so striking, we’re anxious to see FL118 tested in the clinical setting.”

The study’s findings were published online April 2, 2013, in the journal PLOS ONE.

Related Links:
Roswell Park Cancer Institute