On October 21, 2019 Propanc Biopharma, Inc. (OTC: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing new cancer treatments for patients suffering from recurring and metastatic cancer, reported that the mode of action of the company’s lead product candidate, PRP, a formulation consisting of two proenzymes, has been elucidated by the company’s researchers, by suppressing pathways relating to the Epithelial to Mesenchymal Transition (EMT) and metastasis (Press release, Propanc, OCT 21, 2019, View Source [SID1234542386]). The EMT is a biological process by which cells become motile and invasive, but in cancer stem cells (CSCs), results in metastasis, a process whereby secondary tumors are formed often in remote distances from a primary tumor, causing the cancer to return and spread. Scientific data relating to these key findings were published in Scientific Reports, an online open access journal from the Publishers of Nature, entitled, "Pancreatic Proenzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumor engrafting."
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"Our findings from our recently published paper confirms the mechanism of action of PRP, which may prove to be effective tool in the fight against metastatic cancer, the main cause of patient death for sufferers," said Dr Julian Kenyon, Propanc’s Chief Scientific Officer. "By targeting CSCs, PRP is targeting the fundamental mechanism by which cancer spreads, especially after exposure to chemo or radiation, because they are non-dividing cells and are therefore resistant to standard treatments. The mode of action of PRP is complex due to the biological nature of the proenzymes and its multiple modes of action. By defining how it works, it gives us confidence that this treatment method has potential implications in a clinical setting, for example, by reducing recurrence after drug treatment failures in cancer patients."
CSCs have been characterized as immortal cells that grow inside tumours and have a great tumour-initiating capacity. Disturbingly, CSCs have a capacity to remain dormant that make them radio- and chemo-resistant, whilst highly metastatic. As cancer treatment moves towards more personalised medicine targeting specific genes, proper therapies to target and treat specifically CSCs are needed for reducing recurrence after drug resistance failures.
Recently, an exhaustive scientific study with the company’s joint researchers proved that PRP dramatically impairs the maintenance of CSCs characteristics, eradicating these malignant cell populations, even under cell culture conditions that support their enrichment and growth.
The recent study addresses, in depth, the effect of PRP on the cellular mechanism characteristic of pancreatic CSCs. The modulation of hundreds of genes after treatment were analysed and proved the high impact that PRP has on the CSCs population. In fact, the treatment inhibited the expression of genes related to CSCs characteristics, which means that PRP was able to change the nature of these malignant cells toward a more differentiated and less dangerous cellular condition.
From a more detailed scientific perspective, PRP treatment regulates up to four pathways related to cancer spread and metastasis, such as TGFβ, Hippo, Wnt and Notch pathways. The cascade of reactions that PRP imposes on tumour cells, implies the disruption of the CSC characteristics, which reverses the malignant EMT process that leads to tumour invasion.
Furthermore, PRP downregulation of TGFβ-1, had implications in tumour engraftment. In vivo experiments using a nude mice model, in which tumours were induced by inoculation of pancreatic CSCs, showed that PRP impaired CSCs subpopulation activation, niche formation and tumour initiation. In others words, PRP treatment seems to have a preventive effect against cancer. CSCs that were inoculated after treatment with PRP did not find a "comfortable surrounding" where to nest, implying the anticancer potential of this novel drug.
"We continue to make significant progress with our scientific understanding and development of our lead product, PRP, as a targeted cancer stem cell therapy. The global metastatic cancer treatment market is predicted to reach nearly $100 Billion over the next 5-year period, and we believe PRP has the potential to impact the way we view and treat cancer, by minimizing the potential for its return and spread in patients. We have recently completed preclinical development and look forward to advancing PRP into clinical trials in the near future," said James Nathanielsz, Propanc’s Chief Executive Officer.
According to a new market intelligence report by BIS Research, titled "Global Metastatic Cancer Treatment Market – Analysis and Forecast, 2018-2025", the global metastatic cancer treatment market was estimated at $54.11 billion in 2017, and anticipated to reach $98.24 billion by 2025.