An innovative drug with a new mechanism of action that may be effective against a range of cancers will enter the first phase of clinical trials, it was announced today (Monday) at Cancer Research UK's Senior Researchers Meeting.
Cancer Research UK scientists originally designed and developed the drug, SJG-136. Early investigations at the National Cancer Institute in the US have shown that the drug has activity in a broad range of tumour models including breast, ovarian, melanoma, brain, leukaemia and bowel cancer. The first trial will test safety and dose and later trials will evaluate which cancers the drug is most effective against.
SJG-136 offers a new approach for the treatment of cancer. Conventional chemotherapy drugs interact with many areas of DNA to prevent cancer cells reproducing. SJG-136 has the ability to recognize and bind fewer DNA sequences but in a way that may be able to prevent cancer cells reproducing.
Although it is very early in the drug's development, Cancer Research UK scientists believe that SJG-136 offers a new approach for the development of this type of treatment of cancer.
The researchers designed the drug to cross-link the two strands of the DNA double helix at specific sites. This effectively 'handcuffs' certain parts of the DNA – potentially interfering with the cancer cells' reproduction.
The drug has been developed by a partnership between Cancer Research UK, the UK biotech company Spirogen and the National Cancer Institute (NCI) of the US. It has now been licensed to Ipsen, a global pharmaceutical company, which will continue to develop SJG-136.
Professor David Thurston, Director of the Cancer Research UK Gene Targeted Drug Design Research Group at The School of Pharmacy (University of London) and CSO of Spirogen, says: "It has been a long-held goal of drug designers to develop novel compounds that target certain sequences of DNA in cancer cells – and SJG-136 is a unique drug that we think may do this".
"If we find that the regions of DNA we are targeting here are associated with genes instrumental in the development of a tumour, it would be very exciting. There are still many years of research ahead on this project but we are moving forward. We're already developing ideas for how the drug is working at the molecular level."
The trial is sponsored by Cancer Research UK and funded by Ipsen, and will recruit 20 – 30 cancer patients. The aim of this initial trial will be to determine the dose of SJG-136 that can be given safely to patients. This information will hopefully lead to later trials when the drug will be tested against a range of cancers.
Professor Robert Souhami, Cancer Research UK's Director of Clinical and External Affairs, says: "The development of chemotherapy drugs that recognize gene sequences represents the cutting edge of molecular therapeutic research. We have high hopes for this drug but it is very early days and there will be a lengthy process of testing before this drug finally reaches patients." http://www.cancerresearchuk.org
SJG-136 is a low molecular weight DNA sequence-selective cross-linking agent that spans six DNA base pairs with a preference for Pu-GATC-Py sequences. It has substantial anti-tumour activity in over 35 human tumour models so far examined - these include breast, ovarian, melanoma, brain, leukaemia, bowel and glioma.
The Phase I trial will investigate the safety profile of SJG-136 and recommended dose using an intravenous once every three week schedule in patients with refractory solid tumours.
For further details about the trial. Please visit CancerHelp UK.
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