Novel Anticancer Agent May Have Additional Applications in Targeted Therapy

FL118 could be effective in treating late stage cancers.

FL118 could be effective in treating late stage cancers.

The novel anticancer agent FL118 may have additional applications as a personalized therapy for certain tumor types after a recent study showed the drug’s efficacy in treating tumors.

FL118 has previously been found to induce apoptosis by inhibiting the expression of cell-survival proteins. In a recent study published in the American Association for Cancer Research journal Cancer Research, FL118 was found to activate the p53 tumor-suppressor pathway in cancer cells, which encourages cell aging.

The researchers noted that FL118 exhibits potent antitumor efficacy, which suggests additional applications for the drug as a personalized and targeted therapy for certain types of cancer tumors.

An underlying mechanism for the activation of p53 by FL118 was found by researchers in an analysis of preclinical models of colorectal cancer.

“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,” co-lead researcher Fengzhi Li, PhD, said in a press release.

The drug was found to cause the degradation of MdmX, a p53-negative regulator and oncogenic protein, while activating p53 signaling and p53-dependent senescence, in addition to promoting p53-independent apoptosis.

“These unexpected findings open new therapeutic possibilities and support the notion that MdmX depletion is a critical mechanism for activating p53 signaling to control tumor cells,” co-lead researcher Xinjiang Wang, PhD, said in a press release. “We also found that FL118 was particularly effective against MdmX-overexpressing cells.”

The results of the study suggest FL118 can serve as an MdmX-depleting agent in targeted cancer therapies. FL118-based therapy may also be beneficial for a subgroup of cancer patients who have tumors in which MdmX overexpression causes treatment resistance, such as in chronic lymphocytic leukemia and melanomas.

It was concluded that additional research is necessary to analyze how FL118 alters the biochemical properties of the Mdm2-MdmX E3 complex.

FL118 is also being evaluated for the treatment of pancreatic cancer and ovarian cancer.