Science and surgery combine in new lung cancer treatment

A scientist and a surgeon have become experienced inventors, joining forces to forces develop new, more effective treatments for cancer.. Their latest designs for difficult to treat lung cancer will soon go into human trials, and if it works for the patients it could also lead to a commercial success.

Their focus is on a combination therapy that brings in drug combinations and antibodies but the real key is an electrical device that opens up the tumour allowing the drugs to enter and begin damaging the cancer cells.

Dr Declan Soden has a background in genetics and is a principal investigator in University College Cork's Cork Cancer Research Centre and serves as lead scientist for the project. He works with a wide team but his surgical link is with Mr John Hinchion, consultant cardiothorasic surgeon at Cork University.

The challenge they face in tackling lung cancer is daunting. Cork University Hospital sees more than 400 lung cancer patients per year and 85 per cent of them have late stage cancer at time of diagnosis, the researchers say.

It is the fourth most common cancer but is the leading cause of cancer deaths for both men and women. Nationally, there are more than 2,000 new cases each year and these will have a depressingly low five-year survival rate of only 13 per cent.

This serves to spur them on, but also offers hope given the initial successes the two inventors have had with their treatment device, which is based on “electroporation”. For decades researchers have known that if you pass an electric current through tissues it will cause temporary pores to open up on the cell surface, Dr Soden explains.

“The voltage is the key. You need 500 to 1,000 volts per cm, but this is delivered in just one millionth of a second,” he says. “This is very low energy, it doesn’t even warm the tissue but it does destabilise the cell membrane which is held in place by an electrostatic charge. The voltage makes the tissues leaky for about an hour then closes up but this is when the other treatments are applied.”

Having opened up the pores, the team can then apply chemotherapy and a drug that helps kick the immune system into action as a combined attack, not from outside but from within the tumour. These combination therapies enter the tumour while its cells are leaky and then are closed up inside once the pours close, Dr Soden says.

There are huge advantages to this approach, he says. Using electroporation increases the amount of chemotherapy drugs getting into the tumour. "You get up to a 1,000 per cent increase in the chemo absorbed so you can use lower doses causing less of an impact on the patient."

Another advantage is the treatments are done as keyhole surgery with far less surgical healing required. Then there is the use of an immunotherapeutic antibody released in 2012 that holds great promise.

When cancer cells appear the immune system usually steps in and takes them out, but if a cancer takes hold it releases substances that shut down the person’s immune response. The new drug, known as IPI for ipilimumab and developed by Bristol-Myers Squibb, reactivates the immune response, causing the patient’s antibody system to attack the cancer. The effect is very powerful when it takes place within the tumour cells themselves via electroporation.

Two years ago the two researchers won a UCC invention of the year award for their Lung Laparoscopic Electroporation Electrode. They have used various forms of electroporation electrode on about 450 patients so far and they develop a slightly different device depending on the type of cancer involved and where it is located, he says. They work with colleagues in UCC and also with medical device companies in the west to build their prototypes and then test them once cleared for use.

Even using the electrode on its own gave a positive response in 85 per cent of cases treated, he says, and many of these patients had cancers that were resistant to chemo or radiotherapy. They believe that their combination chemo plus IPI applied in conjunction with electroporation will make a real difference in patient response.

The two are awaiting clearance for a human trial from the Health Products Regulatory Authority, the old Irish Medicines Board and hope to be able to start a phase one trial with lung patients in the first quarter of 2015.

Meanwhile, they are advancing the commercial potential for their electroporation devices, taking part on December 2nd in Enterprise Irealnd’s Big Ideas Innovation Showcase event at Convention Centre Dublin. Investors take note.