Experimental drug combination shrinks lab-grown pancreatic tumours

In collaboration with the Press Association

A combination treatment of two experimental drugs could be used to target pancreatic cancers, according to scientists at Stanford University School of Medicine in the US.

"This study forms a strong basis for taking this drug combination forward into clinical trials" - Dr Fieke Froeling

The drugs – called JQ1 and vorinostat – shrank tumours in laboratory mice with the disease, and also killed pancreatic cancer cells grown in the lab.

Both drugs alter the cancer cell’s ability to chemically modify its DNA, which affects the activity of certain genes.

These structural changes to DNA are controlled through a process called epigenetics, which sees different chemical ‘tags’ being added to the DNA. 

And according to Dr Fieke Froeling, an expert in epigenetics and cancer from Imperial College London, drugs that interfere with these processes could be promising for targeting pancreatic cancer.

“This study elegantly shows that so-called ‘epigenetic’ therapies, which target chemically modified DNA, could be a promising treatment for pancreatic cancer, and forms a strong basis for taking this drug combination forward into clinical trials,” she said.

Cases of pancreatic cancer can usually be linked to faults in an important gene called KRAS, which makes a protein that is essential for controlling how cells grow. But researchers have struggled to develop drugs to target this faulty molecule.

“Much of the recent focus in research on pancreatic cancer has been on drugs that target specific genetic faults,” said Fieke. 

“But thanks to increased insights and knowledge of the epigenetic changes occurring in pancreatic cancer, it now looks like targeting these processes could help shift some of the dismal statistics often associated with this disease,” she added.

Taking the epigenetic approach, the Stanford team tested multiple drugs in combination with JQ1 – a drug that affects a cell’s ability to sense particular chemical ‘tags’. 

When they combined JQ1 with vorinostat – another epigenetic drug – they saw that pancreatic tumours shrank in mice, increasing the survival time of the animals.

"It happened that the drug that worked best was another epigenetic drug called vorinostat," said study author Professor Julien Sage. "On its own, vorinostat didn't work very well, but when combined with JQ1 it showed a very strong synergistic effect in both the laboratory mice with pancreatic cancer and in pancreatic cancer cells from people with the disease."

The authors hope the newly identified combination treatment can be tested in early phase clinical trials within the next five years.

References

  • Mazur, P., et al. (2015). Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma Nature Medicine DOI: 10.1038/nm.3952