Researchers from Melbourne’s Peter MacCallum Cancer Centre have discovered a new drug which stops tumour growth and strengthens the power of chemotherapy in laboratory models of advanced oesophageal cancer, paving the way for clinical trials for people with this serious form of cancer.
Oesophageal cancer affects 1,450 Australians each year and standard treatment, a combination of chemotherapy and radiation therapy followed by surgery, is curative in only 10–20 per cent of patients; the remainder invariably relapse within months or a few years, at which time no standard treatment options are reliably effective.
Professor Wayne Phillips, co-author of the research released in the scientific journal ‘Gut’ overnight, says the potent efficacy of novel drug APR-246, provided by Aprea AB, Sweden, in patient-derived laboratory models provides new treatment hope for 80 per cent of oesophageal cancer patients.
‘Four out of five people with oesophageal cancer carry a mutation in the powerful p53 protein, removing the ability of this protein to suppress the growth of tumours.
‘In our laboratory models, which use human tissue taken from patients during surgery – an approach Peter Mac is moving towards as standard, as opposed to the traditional use of models using cell lines – we found APR-246 reactivated the ability of p53 to block tumour growth.’
Professor Phillips says the research is promising because APR-246 delivered a synergistic benefit with chemotherapy, and the drug has proven safe in human trials of other cancers.
‘The effect of APR-246 was stronger when combined with standard chemotherapy, giving us confidence that clinical trials for people with advanced disease might be fast-tracked to try and stall the growth of their tumours.
‘Because it affects mutant p53, which is not found in normal healthy cells, APR-246 carries the added benefit of only targeting cancer cells, reducing the potential for toxic side effects.
Indeed, minimal side effects of APR-246 have been noted in early human trials in ovarian, hematological and prostate cancer.’
Professor Phillips says as people can be tested for the presence of mutant p53, patients could be optimally selected for the new treatment approach in future.
The research was also led by Dr David Liu and Dr Nicholas Clemons from Peter Mac’s Surgical Oncology Research Laboratory, with support from the National Health and Medical Research Council’s Centres of Research Excellence and in partnership with researchers from Sweden’s Karolinska Institute.