ASX-listed clinical-stage oncology group, PharmAust has extended its pre-clinical studies collaboration with the Olivia Newton-John Cancer Research Institute as they continue to work towards determining how effectively PharmAust’s Monepantel drug combats cancer cells.
Researchers at the Cell Death and Survival Laboratory at the Melbourne-based Olivia Newton-John Cancer Research Institute, or “ONJCRI” have been investigating the response of the entire genome of cancer cells to treatment with Monepantel, using the RNA sequencing screening process.
PharmAust explained the RNA sequencing screening identifies which genes are switched on and which genes are switched off by Monepantel. Last year the ONJCRI used a non-cancer cell line as a control, while melanoma, lung cancer and ovarian cancer were the three cancer cell lines.
The ONJCRI researchers found that changes in the gene expression in the non-cancer cell genome were relatively modest compared with changes encountered in the three cancer cell lines. PharmAust says this supports previous studies indicating Monepantel does not affect non-cancer cells, and encouragingly, has selectivity towards cancer cells.
According to PharmAust, the independent ONJCRI testing demonstrated that cancer cell genes involved in promoting the division and proliferation of cells were suppressed, while those involved in the death or self-destruction of cells were induced.
Results to date have been consistent, PharmAust says, with other data showing Monepantel acts to stop the growth in the spread of cancer cells and causes them to self-destruct.
PharmAust Chief Scientific Officer, Dr Richard Mollard said last year: “It is terrific to have independent confirmation of Monepantel’s specificity to cancer cells as well as a comprehensive dissection of the genetic pathways associated with Monepantel’s anti-cancer action. This systematic work will facilitate PharmAust’s applications for human clinical trials with regulatory agencies such as the TGA in Australia, the FDA in the US and the EMA in Europe, particularly as it demonstrates the selective nature of how MPL may operate physiologically.”
The ONJCRI researchers will now examine in greater detail the select subset of genes identified in the screening and look to match changes in their activity with changes in associated protein signalling pathways.
PharmAust and the ONJCRI hopes to find out what happens within cancer cells once Monepantel interacts with their primary molecular targets and then exerts its anti-cancer activity.
Establishing Monepantel’s mechanism of action will help differentiate Monepantel’s effects on cancer cells against other cancer-fighting drugs, which will assist in regulatory submissions and facilitating licensing and marketing as it progresses to human clinical trials.
Dr Mollard said: “PharmAust is looking forward to seeing at the molecular level how Monepantel works in cells to combat disease, especially in terms of how Monepantel’s mechanism of action differs to other mTOR inhibitors presently in the clinic.”
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