Clinical-stage oncology company PharmAust (ASX: PAA) has announced the Olivia Newton-John Cancer Research Institute (ONJCRI) is investigating the anti-cancer mechanism of its flagship drug candidate monepantel.
ONJCRI’s work is being partly supported by a $50,000 Innovation Connections grant from the federal government’s Department of Industry, Innovation and Science.
It involves researchers in the centre’s Cell Death and Survival Laboratory conducting an RNA sequencing screen to evaluate how the entire genome of cancer cells respond when treated with the drug. In particular, the approach is expected to identify which genes are “switched on” and which are “switched off” by monepantel.
Three cancer cell lines were melanoma (skin cancer), lung cancer and ovarian cancer are being evaluated while another non-cancer cell line is used as a control.
Gene candidates identified for further investigations
According to PharmAust, the ONJCRI researchers found changes in gene expression in the non-cancer cell genome were “relatively modest” when compared to the changes in the three cancer cell lines.
“This observation supports previous studies indicating that monepantel does not affect non-cancer cells and has selectivity towards cancer cells,” the company stated.
“Particularly, the ONJCRI demonstrated that cancer cell genes involved in promoting cell division were suppressed, while those involved in inducing cell death (apoptosis) or autophagy were induced,” PharmAust added.
It said the observations are consistent with other data that shows monepantel acts to stop cancer cells from dividing and to self-destruct.
The genes identified from the screen will now be investigated further to establish the mechanism of action of monepantel and to enable differentiation of the drug’s effects on cancer cells compared to other anti-cancer drugs.
Research will aid human clinical trial applications
PharmAust chief scientific officer Dr Richard Mollard said the company is delighted to have independent confirmation of monepantel’s specificity to cancer cells, as well as a comprehension dissection of the genetic pathways associated with the drug’s anti-cancer action.
“This systematic work will facilitate PharmAust’s applications for human clinical trials with regulatory agencies such as the Therapeutic Goods Administration (TGA) in Australia, the Food and Drug Administration (FDA) in the US and the European Medicines Agency (EMA) in Europe, particularly as it demonstrates the selective nature of how monepantel may operate physiologically,” he added.
ONJCRI investigates and develops treatments for cancers of the breast, bowel, lung, skin, prostate, liver, gastrointestinal tract and brain. The centre is named after Dame Olivia Newton-John, an Australian actress who is currently battling stage four metastatic breast cancer.