The drug, a collaboration of The Institute of Cancer Research (ICR) and Chroma Therapeutics, is aimed at errors that cause cancer in the way the body reads the DNA code, instead of targeting the faults in the DNA code.
Reading cancer-causing errors in the way the body reads the DNA code is a very significant set of instructions, that focuses on a number of chemical switches, which determine whether or not genes are switched on or off and ultimately determines the cell's function and its appearance. Changes in epigenetic control can also lead to cancer.
Leading researcher, Dr Udai Banerji from the ICR and The Royal Marsden explains:
"This is a new angle of attack against cancer. Scientists are already working hard to design drugs that target many cancer genes, but there is also huge potential in targeting these epigenetic changes. Although epigenetics is a normal part of biology, faults in epigenetic switches can cause cancer by switching on oncogenes or switching off tumor suppressing genes."
The new drug targets an enzyme called histone deacetylase (HDAC) that generally controls gene expression by switching genes on and off through modifying histones, i.e. the proteins that package and order DNA.
From the entire range of known epigenetic targets, the largest progress has been achieved in developing HDAC inhibitors. Two HDAC inhibiting drugs are already licensed for the treatment of a certain type of lymphoma although these drugs have limitations in terms of having considerable adverse effects and one of these drugs requires injections.
CHR-3996, the next-generation HDAC drug has been developed to inhibit one type of HDAC enzyme (class one) in particular, and the research team hopes this will decrease adverse effects in existing treatments without diminishing its anti-cancer properties. In lab tests they observed that the drug managed to kill various different cancer cell types.
The team evaluated CHR-3996's efficacy in a Phase I study, which took place in the Drug Development Unit of the ICR at the Royal Marsden in the UK and at the Erasmus University Medical Center in Rotterdam, The Netherlands.
Dr Banerji states:
"First-generation HDAC inhibitors have already demonstrated that this class of drugs can be effective for some cancer patients. The objective here was to develop a more specific drug that would be better tolerated, and could be formulated so it can be administered as tablets rather than an injection to maximize patient comfort and safety. We found that CHR-3996 was active when taken in pill form, and the side-effects were favorable."
The trial's primary goal was to evaluate CHR-3996's safety. The team observed that one patient's pancreatic tumors had shrunk, whilst nine others were seen to be stable for at least two months. According to blood tests, the drug achieved its target and was observed to be in a concentration in the patients' body, which was enough to result in tumor shrinkage in pre-clinical models.
Within the last 5 years, CHR-3996 is one of 16 innovative drug candidates that have been discovered in the ICR's Cancer Research UK Cancer Therapeutics Unit, as well as one of six drugs that were managed to into Phase I clinical trials at the ICR and The Royal Marsden's Drug Development Unit.
According to Professor Paul Workman, Director of the Cancer Research UK Cancer Therapeutics Unit at the ICR:
"It very gratifying to see promising results from the first stage of clinical evaluation for this epigenetic drug, which was discovered through a collaboration between Chroma Therapeutics and The Institute of Cancer Research. We are looking forward to seeing the results of larger-scale patient trials."
Dr Joanna Reynolds, director of Cancer Research UK's centers, commented:
"This 'epigenetic' approach to therapy - which targets chemical switches rather than DNA - is an exciting new avenue for drug discovery and it's great to see rapid progress being made in this field. We look forward to seeing the results of further trials, which will aim to discover whether this pill can help improve cancer survival in patients with advanced disease."
Written By Petra Rattue