Each year, more than 4,000 Australians are diagnosed with pancreatic cancer, a form of cancer which is difficult to diagnose and with limited treatment options. Thanks to a new study conducted by the Garvan Institute of Medical Research, however, a drug developed by biotech company Pharmaxis (ASX: PXS) could increase patient survival rates by 35%.
The Garvan Institute study examined PXS-5505, a pan-Lysyl Oxidase (pan-LOX) inhibitor that has already demonstrated groundbreaking potential in cancer having reported Phase 2 clinical trial results in humans diagnosed with myelofibrosis (bone marrow cancer).
In their preclinical study targeting pancreatic cancer, the Garvan Institute examined PXS-5505 and its anti-fibrotic properties due to the prevalence of fibrotic scarring on the pancreas in advanced stage diagnosis. As well as the 35% improvement in survival the study conducted in mouse models also showed that PXS-5505 combined with chemotherapy reduced the spread of pancreatic ductal adenocarcinoma to other organs such as the liver by 45%.
Pancreatic ductal adenocarcinoma is one of the most aggressive forms of pancreatic cancer with a five-year survival rate of less than 10% under the current standard of treatment.
Findings of the study have been published in the prestigious journal Nature Cancer, led by Associate Professor Thomas Cox, head of the Matrix & Metastasis Lab at Garvan. Many pancreatic cancers develop chemotherapy resistance soon after treatment starts, which contributes to the poor survival of patients. Part of this resistance is driven by tumour fibrosis forming excess scar tissue around pancreatic tumours that in turn reduces the effectiveness of chemotherapy drugs.
“The preclinical validation of this first-in-class anti-fibrotic drug marks a major milestone in the quest to overcome the significant challenges in treating pancreatic cancer and brings hope to patients and their families,” said Associate Professor Cox.
PXS-5505 is an anti-fibrotic pan-LOX inhibitor that has not only completed long-term toxicity studies but has also successfully passed Phase 1a and 1b clinical trials, establishing itself as a well-tolerated drug. The inhibitor effectively targets all enzymes within the lysyl oxidase family, which are known to play a crucial role in fibrosis.
Fibrosis occurs as a result of prolonged tissue damage and inflammation, leading to the accumulation of excess collagen and other extracellular matrix components. This process can severely disrupt the normal structure and function of organs, ultimately impairing their ability to perform vital functions. In the context of cancer, fibrosis can create a favourable microenvironment for tumour growth by providing a scaffold for cancer cells to proliferate and enabling the cancer to evade the immune system.
The implications of this study are substantial. By inhibiting lysyl oxidase enzymes, PXS-5505 suppresses the crosslinking of collagen fibres, thereby reducing the stiffness of the tumour microenvironment. This makes it more difficult for cancer cells to thrive and spread. Furthermore, inhibiting fibrosis can potentially improve drug delivery to tumour cells, as fibrotic tissue can hinder the penetration of chemotherapy agents into the tumour.
As the discoverers of PXS-5505, Pharmaxis continues to benefit from major interest in the drug’s anti-fibrotic properties which has repeatedly indicated an ability to modify cancer by inhibiting LOX enzymes.
“We have already seen very promising early results in a Phase 2 trial with patients that have the bone marrow cancer myelofibrosis,” said Pharmaxis CEO, Gary Phillips.
“This latest ground-breaking research stems from a long collaboration with the team of high calibre researchers at the Garvan Institute and provides exciting new evidence that PXS-5505 may also have a role as a therapy to improve the effect of current chemotherapy drugs in solid tumours like pancreatic cancer and extending the life of patients.”
While the results of this preclinical study are promising, further research is needed to validate these findings in human clinical trials. If successful, PXS-5505 could offer a groundbreaking approach to treating pancreatic cancer.
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