Pancreatic cancer drug targets scar-like tumour tissue

Drug development company Pharmaxis has announced the publication of preclinical results showing its anti-fibrotic drug, named PXS‐5505, increases survival by 35% compared to chemotherapy treatment alone in the treatment of pancreatic ductal adenocarcinoma — one of the most aggressive forms of pancreatic cancer.

Pancreatic cancer is often diagnosed at an advanced stage, which means that chemotherapy is usually the only treatment option available. Many pancreatic cancers develop chemotherapy resistance soon after treatment starts, contributing to a five-year survival rate of less than 10%. Part of this resistance is driven by tumour fibrosis forming a mesh of scar tissue within and around pancreatic tumours that in turn reduces the effectiveness of chemotherapy drugs.

PXS‐5505 is a pan‐lysyl oxidase (pan‐LOX) inhibitor that blocks the enzymes that are critical for the deposition of collagen into the fibrotic tissue. It has completed long‐term toxicity studies and Phase 1a and 1b clinical trials, demonstrating a well‐tolerated drug that effectively inhibits all enzymes in the lysyl oxidase family that are involved in fibrosis.

“PXS‐5505 returns the tumour microenvironment to a more ‘normal’ state by reducing fibrosis and decreasing tumour stiffness,” said Dr Jessica Chitty, Senior Research Officer at the Garvan Institute of Medical Research. “This allows chemotherapy drugs to penetrate the tumours more easily, work more effectively and destroy more cancer cells.”

In collaboration with Pharmaxis, Chitty and her fellow Garvan researchers led a study which found that the drug significantly reduced fibrosis in pancreatic tumours in mouse models. Their research showed that, when given in combination with chemotherapy, PXS-5505 increased survival time by more than 35% compared to chemotherapy treatment alone, and also reduced the spread of the cancer to other organs, such as the liver, by 45%. Their results were published in the journal Nature Cancer.

“We have already seen very promising early results in a phase 2 trial with patients that have the bone marrow cancer myelofibrosis,” said Pharmaxis Chief Executive Gary Phillips. “This groundbreaking 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.”

“The preclinical validation of this first-in-class anti-fibrotic drug marks a major milestone in our quest to overcome the significant challenges in treating pancreatic cancer and brings hope to patients and their families,” said Associate Professor Thomas Cox, Head of the Matrix & Metastasis Lab at Garvan and senior author of the study.

“We are now in the process of progressing this work toward clinical trials that will evaluate this promising drug combination approach for pancreatic cancer patients.”

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