Research And Grants

Facilitates Chromatin Transcription Complex (FACT): A novel therapeutic target against Diffuse Intrinsic Pontine Glioma.

This project aims to test the hypothesis that targeting complex known as FACT (Facilitates Chromatin Transcription) represents a novel therapeutic approach for Diffuse Intrinsic Pontine Glioma (DIPG) and our objective is to develop effective combination strategies optimal for clinical translation.

The specific research aims listed in the previously--‐ submitted TCSN project proposal are:

• To examine the anticancer properties of CBL0137 in a panel of DIPG neurospheres.
• To evaluate the mechanism of action of CBL0137.
• To examine combination therapies which enhance the activity of CBL0137 against DIPG in vitro.
• To determine the therapeutic effect of CBL0137 as a single agent, with most effective combination (double agent combination) and with currently used treatment irradiation (triple combination) in vivo. A larger grant was submitted to the NHMRC to comprehensively investigate the FACT complex as a therapeutic target in DIPG and Neuroblastoma, evaluate efficacy for a COG Phase I/II paediatric clinical trial and identify biomarkers.

The specific aims of this project are:

(1) To investigate the potential of high FACT expression, and other specific biomarkers to predict and monitor CBL0137 response in DIPG and neuroblastoma.

(2) To evaluate combination therapies which enhance the ability of CBL0137 to inhibit DIPG and neuroblastoma proliferation in vitro.

(3) To evaluate the efficacy of CBL0137 in combination with chemotherapeutic drugs using in vivo models of DIPG and neuroblastoma.

(4) To assess biomarker efficacy by undertaking correlative biology studies on clinical specimens from patients treated in a Phase I/II clinical trial of CBL0137.