Cardiff University researchers developing new anti-cancer stem cell compound

By Al Saint Jacques, MDLinx
Published December 17, 2015

Key Takeaways

A novel anti-cancer stem cell agent capable of targeting aggressive tumour-forming cells common to breast, pancreas, colon, and prostate cancers is being developed by researchers at Cardiff University in Wales, according to a university news release. Pre-clinical studies have shown it to be effective in eliminating a number of different kinds of cancers cells, including cancer stem cells from human breast cancer patient biopsies. This new OH14 compound has been licensed by Tiziana Life Sciences, a British-based pharmaceutical company and will now undergo further development before proceeding to clinical trials.

The breakthrough comes almost exactly a year after the same research team announced that they had discovered a molecule capable of reversing the spread of malignant breast cancer, according to the release. The multidisciplinary team is comprised of researchers based in the University's European Cancer Stem Cell Research Institute (ECSCRI) and the School of Pharmacy and Pharmaceutical Sciences.

Last January, state-of-the-art computer aided modeling enabled the researchers to identify an anti-cancer agent capable of deactivating a gene known to be essential for the metastatic spread of breast cancer. Using the same computer-based approach, the team has now been able to target the c-FLIP (cellular FLICE [FADD-like IL-1β-converting enzyme]-inhibitory) protein, known to play a key role in cancer stem cell maintenance and survival, described in previously published work by the Institute.

"Our computer-aided drug screening process has now identified two new classes of anti-cancer agents, specifically targeting two distinct and novel mechanisms underpinning cancer," said Dr Andrea Brancale from Cardiff's School of Pharmacy and Pharmaceuticals, who led the team that designed the compound.

According to the study findings, targeting c-FLIP with the OH14 compound works on two fronts: first by helping to deactivate the tumour's self-defense mechanism against the immune system and second to prevent its regrowth. The main function of the c-FLIP protein is to prevent the TNF-related apoptosis-inducing ligand (TRAIL) from killing cells. TRAIL is a naturally occurring and crucial molecule that is used by the body's immune system to kill damaged or cancerous cells.

The researchers hope that ultimately human trials will prove the efficacy of the OH14 compound in sensitising tumour cells and cancer stem cells to existing drug-based therapies thus disabling tumours from seeding new growth after treatment.

The new compound is the first experimental anti-cancer stem cell agent to have emerged from the European Cancer Stem Cell Research Institute. Having acquired the licence for its commercialisation, Tiziana Life Sciences has committed funding for ongoing research that will focus on drug development.

"We are delighted to extend our relationship with Tiziana Life Sciences. OH14 is an example of a new generation of experimental agents designed to selectively target the pernicious stems cells within a tumour, thus improving the long-term prospects of cancer patients," explained Dr. Richard Clarkson, lead researcher on the c-FLIP project and senior researcher at the University's ECSCRI.

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