Newswise — BUFFALO, N.Y. — There has been great progress in recent decades in the treatment of pediatric cancers, with high cure rates possible today for several childhood malignancies. Prognosis remains poor, however, for children diagnosed with a number of pediatric cancers, and many existing therapies are associated with long-term side effects that impact survivors’ life expectancy and/or quality of life. Writing in the journal Science Translational Medicine, an international team of scientists from the Children’s Cancer Institute–Australia (CCIA), Roswell Park Cancer Institute (RPCI) and Incuron LLC report significant progress toward addressing these persistent challenges.

The CCIA’s Daniel Carter, PhD, Glenn Marshall, MD, and co-authors report that they have identified a new treatment approach for a highly aggressive and usually fatal subtype of neuroblastoma, a cancer of nerve cells that is one of the most frequent solid tumors in children. The researchers provide evidence that the protein complex FACT (facilitates chromatin transcription) represents a new and promising biomarker candidate and a target for treatment of this aggressive, treatment-resistant disease. They observe that a FACT-targeting drug candidate — CBL0137, which was developed by the biotech company Incuron in collaboration with scientists from RPCI — has demonstrated significant antitumor activity in preclinical models of neuroblastoma.

CBL0137 is a small molecule that belongs to a class of agents called curaxins, which were invented by a group that included paper co-author Andrei Gudkov, PhD, DSci, Senior Vice President for Basic Science at Roswell Park and founder and Chief Scientific Officer of Incuron.

“This work, which beautifully demonstrates the power of international collaboration of oncology researchers working both at academic centers and private enterprises, gives us hope that we will see improved cure rates and long-term outcomes for children afflicted with this aggressive disease,” says Dr. Gudkov. “We hope to soon be able to extend the opportunity to participate in clinical studies of curaxin CBL0137 to children with neuroblastoma, a prospect we eagerly await given the limited treatment options available currently.”

While another target for this subtype of neuroblastoma, the MYC oncogene, exists, efforts to effectively reach this target by pharmacological agents have so far proven unsuccessful. The study in Science Translational Medicine for the first time demonstrates that MYC activity in these tumors depends on the presence of FACT and that inactivation of FACT effectively neutralizes MYC, resulting in the death of neuroblastoma cells.

“Remarkably, the presence of FACT in this type of tumor appeared to be as bad a prognostic marker as excessive activity of MYC is,” notes paper co-author Katerina Gurova, MD, PhD, of the Roswell Park Department of Cell Stress Biology, who led efforts to decipher the mechanisms of activity through which curaxins successfully target FACT, as documented in earlier published research.

CBL0137, which is being developed by Incuron, is currently being assessed in a phase I clinical trial in adults with advanced metastatic solid-tumor cancers and lymphomas at RPCI and several other U.S. cancer centers (study NCT01905228). As distinct from many of the drugs currently used to treat neuroblastoma, curaxins appear to kill cancer cells without causing DNA damage, the major source of cancer treatment side effects.

This work was funded in part by grants from Incuron LLC to some authors. The researchers also credit early funding from the Roswell Park Alliance Foundation as critical to these latest efforts.

The paper, “Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma,” is available online at

About RPCI:The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. Founded in 1898, RPCI is one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit, call 1-877-ASK-RPCI (1-877-275-7724) or email [email protected]. Follow Roswell Park on Facebook and Twitter.

About Incuron LLC:Incuron LLC is an innovative biopharmaceutical company seeking to develop first-in-class pharmaceuticals designed to address diseases with significant medical need. Curaxin CBL0137 is Incuron’s lead oncology product candidate. Incuron holds worldwide development and commercialization rights to CBL0137. The company conducts business in the United States and in the Russian Federation. To learn more about Incuron LLC, please visit the company’s website at

About Curaxin CBL0137:CBL0137, Incuron LLC’s lead oncology product candidate, is an investigational oncology drug that targets cancer cells by inhibition of the histone chaperone FACT (Facilitates Chromatin Transcription). The interaction of CBL0137 with FACT complex results in simultaneous NF-kB suppression, heat-shock factor 1 suppression and p53 activation. This modulation of three key cellular pathways causes suppression of cancer cell growth. CBL0137 has been shown in preclinical studies to have anti-cancer effects in multiple solid and hematological tumor animal models. The safety, pharmacokinetics and pharmacodynamics of oral and intravenous formulations of CBL0137 are currently being investigated in two ongoing Phase 1 clinical studies in patients with advanced solid tumors. To date, no dose-limiting toxicities have been observed with either oral or intravenous administration through the highest CBL0137 dose levels tested. Incuron LLC holds worldwide development and commercialization rights to CBL0137.

About the Children’s Cancer Institute–Australia:Children’s Cancer Institute is the only independent medical research organisation in Australia dedicated 100% to childhood cancer research, existing solely to cure childhood cancer and improve the quality of life for survivors. The Institute was originally known as The Children’s Leukaemia and Cancer Foundation and was established in May 1976 by a dedicated group of parents and doctors of children with cancer. Children’s Cancer Institute opened its own research laboratories in 1984 and has since grown to employ nearly 200 staff and students, establishing a national and international reputation for scientific excellence. For more information, visit