Skip Content

Modified virus can prevent resistance to chemotherapy

11 May 2016

New research funded by Pancreatic Cancer Research Fund has shown that an altered version of the flu virus could be used to overcome pancreatic cancer’s resistance to certain drugs – and improve how those drugs work.

The study, conducted at Barts Cancer Institute, Queen Mary University of London (QMUL) contributes to a growing area in cancer treatment in which viruses are harnessed to kill cancer cells.

Viruses can be modified to target and infect only cancer cells, leaving healthy cells unharmed. These viruses use cancer cells as a factory to generate thousands of new viruses, and continue to replicate until the cell bursts. The virus copies will then spread and infect surrounding tumour cells and repeat the process. 

While virotherapy is a very exciting approach, there are still some limitations; for example, the body’s immune system will usually kill off the virus before it can infect all the cells within a tumour. Because of these challenges, many researchers are looking at ways that virotherapy can be used in combination with existing treatments to support or boost their effect. 

In the PCRF-funded study, published in the journal Oncotarget, the team at QMUL made a genetic modification to a virus called adenovirus, to give it an extra weapon. They then tested it on pancreatic cancer cells that had been treated with gemcitabine, a common chemotherapy drug used to treat pancreatic cancer.

Gemcitabine works by damaging the DNA in the cancer cells, which prevents them from dividing and causes them to die. Over time, however, the cancer cells become resistant to the drug by repairing the damage to its DNA, allowing them to continue to divide and spread.

The Barts researchers showed that the altered virus could infect and replicate inside the pancreatic cancer cells as expected, but they also found that it stopped the cancer cells from repairing the DNA damage caused by the gemcitabine. This allowed the gemcitabine to work more effectively - and crucially,  prevented the cancer cells from becoming resistant to the drug.

“Many cancers – including pancreatic cancer – become resistant to treatments like gemcitabine, and currently there’s no way to get round that,” explains Dr Gunnel Halldèn, who led the research. “The virus that we have modified ‘re-sensitises’ the resistant cancer cell by preventing the cell from repairing itself. The virus alone will kill some tumour cells, but in combination with the drug, the number of cells that are killed is greatly increased.”

This research is at an early stage because the modified virus has only been tested on pancreatic cancer cells in the laboratory, but the team believe they may have found a promising new opportunity for developing combination treatments for pancreatic cancer.

Dr Hallden added: “Because the virus improves the effectiveness of the drug, it means it could also be possible to use lower doses, which would also reduce the unpleasant side-effects associated with chemotherapy,”  she added.

The next step for the researchers will be to test other altered versions of adenovirus to better understand the exact mechanism through which it enhances cell killing. Further modifications will also be made to enable the virus to harness the body’s immune system to attack any cancer cells that have not been infected by the virus.

Dr Gunnel Hallden

< Back