The FACT complex is involved in chromatin remodeling during transcription, replication, and DNA repair. These studies confirm an association between FACT and cancer by showing that FACT is expressed at higher levels in tumor cell lines than in normal cells in vitro and that elimination of FACT expression leads to reduced growth and decreased survival of tumor cells. The published work concludes that FACT’s role in cancer likely involves selective chromatin remodeling of genes that stimulate proliferation, inhibit cell death and differentiation, and regulate cellular stress responses, making it an enabler of oncogene-induced transformation.
In addition, the studies establish a statistically significant association between the frequency and level of FACT expression and tumor aggressiveness. The studies demonstrated that FACT is predominantly expressed in aggressive undifferentiated cancers that result in poor overall patient survival because of the development of metastatic disease, irrespective of tumor size at the time of diagnosis. This increases the potential value of FACT as a prognostic marker, as FACT positivity of a primary tumor could be used at a very early stage to determine the risk of future metastatic disease.
“This recent publication builds upon our previous work showing that FACT is the molecular target of Curaxins,” noted Katerina Gurova, M.D., Ph.D., a researcher in the Department of Cell Stress Biology at RPCI and lead author. “The data presented in the Cell Reports publication indicate that FACT is a promising marker and target for subtypes of cancer characterized by high grade and aggressiveness, and poor prognosis. This, together with the absence of FACT expression in most normal tissues, suggests that pharmacological inhibition of FACT using Curaxins could be an effective strategy to treat types of cancer for which there are currently few treatment options.”
Jean Viallet, M.D., Chief Development Officer at Cleveland BioLabs, stated, “We are evaluating the enormous body of data collected by our collaborators on FACT expression and its role in cancer progression in an effort to focus our next trials with our lead Curaxin drug candidate, CBL0137. Our plan is to enrich the upcoming study of the intravenous administration of CBL0137 in patients with metastatic or unresectable advanced solid tumors and lymphomas by including patients whose tumor types are dependent on transcriptional oncogenes.”
In March 2013, a Notice of Allowance was received from the U.S. Food and Drug Administration for an Investigational New Drug Application for intravenous administration of CBL0137. A Phase 1 single-agent dose-escalation study of oral administration of CBL0137 in patients with advanced solid tumors that are resistant or refractory to standard-of-care treatment is ongoing in the Russian Federation.
The Cell Reports publication may be found online at: http://cellreports.cell.com/.