A team of scientists at the University of St Andrews have used a genetic screening approach to investigate a potential new cancer treatment.
Gemcitabine is a chemotherapy agent used as a mainstay of treatment for pancreatic, ovarian, lung and breast cancers, amongst others. Despite its widespread use, gemcitabine achieves responses in less than 10% of patients with metastatic pancreatic cancer and has a very limited impact on overall survival.
Now a team from the School of Medicine at the University of St Andrews have used a genetic screening approach to investigate a new drug, NUC-1031, which delivers the same active anti-cancer metabolite as gemcitabine but at much higher concentrations and for a longer period.
The research, published in Scientific Reports (Tuesday 21 May), demonstrates several advantages of NUC-1031 over gemcitabine, which has clinical implications and could revolutionise cancer treatment in patients.
The clinical relevance of these findings was tested by using two patient cohorts, one treated with gemcitabine, the other with NUC-1031. The research demonstrated that the clinical activity of gemcitabine might at least, in part, rely on expression of a biomarker called Deoxycytidine kinase (DCK), this was not the case for NUC-1031. Importantly, patients who had previously relapsed on gemcitabine treatment showed clinical responses to NUC-1031, further confirming the potential for NUC-1031 to represent a more effective treatment option for these patients.
Lead scientist, Dr Paul Reynolds from the School of Medicine said: “Overall, our data support the use of the ProTide NUC-1031, even in gemcitabine-resistant cancers. This is a great example of how academia can help pharma in progressing their drug pipelines and contribute to the process of providing new treatment options to patients.”
This study was supported by a Medical Research Scotland PhD studentship in association with NuCana plc.
The paper Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031 is published in Scientific Reports and is available online.
Please ensure that the paper’s DOI (http://dx.doi.org/10.1038/s41598-019-44089-3) is included in all online stories and social media posts and that Scientific Reports is credited as the source.
Issued by the University of St Andrews Communications Office.Research