Article: Viruses set to 'kill' cancer

Interview with Doctor Frank Giles

From the Irish Medical Times
http://www.imt.ie/news/2008/03/viruses_set_to_kill_cancer.html
by Gary Culliton

Galway-born Dr Frank Giles is responsible for cancer care in a much larger population than the entire island of Ireland. He heads up functional clinical cancer services for many millions of people in Texas as Chief of the Division of Haematology and Medical Oncology at the San Antonio Cancer Institute. These include radiation oncology and surgical oncology.

“To me, the concept of Ireland as discrete units, rather than one functioning medical complex, doesn’t bear any approximation of the reality of the world now,” he told Irish Medical Times before receiving the Medtronic Award for Healthcare & Medical Science from NUI Galway recently.

Viruses are hard to kill and for this reason, Dr Giles’ team is working towards targeting them at cancer. Part of the reason a virus attacks in particular places in our body at certain times, depends on the metabolic state of the cells.

“If a virus likes to infect cells that have a specific kinase pattern, maybe we can find cancers that preferentially have that profile. We now have administered a virus to humans as an anti-cancer agent,” Dr Giles said. “There have been sufficient responses in the first cohort of 12 people to expand the study.” Dr Giles is working on three anti-cancer viruses: GT-111, Reolysin and SVV-001.

Kinase activation
Dr Giles’ team will be publishing a paper on the subject shortly. The fairly benign virus reolysin likes to infect and kill the cells of one difficult-to-treat sarcoma – a nasty solid tumour with a particular kinase activation. Dr Giles’ team in San Antonio has treated an initial 12 people with this virus.

“At least one is responding and some others have stable disease, so we’re expanding the study. It’s very early, we don’t even know how much is a good dose of the virus to administer. But it’s a whole new world. In this new century, we may be able to turn these traditional enemies of ours to our advantage,” he said. Another virus is designed to switch off or kill the new blood supply which metastatic tumours subtend to themselves.

Dr Giles is also the Director of the Experimental Therapeutics Program at the San Antonio Cancer Institute. He has pioneered the use of many agents that are now in regular use as targeted therapies for patients with cancer. He has focused his clinical and research efforts on providing therapy for patients suffering from treatment-resistant or refractory cancer. His interests include lymphomas, multiple myeloma, developmental therapeutics, stem cell transplantation and leukaemias.

Cell population needed
Even in tumours where there is very high percentage cell ‘kill’ following therapy, that does not equate to cure. “We know that there is a very small percentage of cancer cells that are capable of propagating and keeping the tumour alive,” Dr Giles said. “That is the cell population which you need to eliminate. Quite often, they have subtle but important differences from their progeny.”

In the next ten years, it is thought that we will see cancer treatment move away from long-term remission to targeted cures. Hard-to-access cancer stem cells are the final barrier to a very significant increase in the cure rate. These cells are the last grouping which needs to be understood, in order to cure a lot more people. The impact of Dr Giles’ work in this area will be felt in general clinics within five years.

Following his work in the areas of leukaemia, lymphoma and myeloma, Dr Giles is now focused more on the solid tumours like sarcoma and ovarian cancer. “As the therapy changes, the old divides between histology – what a solid lump of tumour looks like versus a leukaemia – are becoming much less important than what actually drives the cancer,” Dr Giles said.

Chronic myeloid leukaemia and a gastro-intestinal solid tumour (GIST) look as different as night and day. However, both are driven by molecular abnormalities that are sensitive to the same drug Gleevec (imatinib) that Dr Giles was involved in developing. Pathology is as important as ever, but disorders which may not be remotely alike may be susceptible to a common mode of attack. Agents can target kinase cell-proliferating enzymes. These are modulated in normal tissue. Genetically, these are driven hyper-active in a tumour.

Dr Giles left Galway, where he had worked, almost 20 years ago. He went to St James’s Hospital in Dublin, then to London, to Chapel Hill in North Carolina and then to UCLA in California. He has been in Texas for 11 years.

“We can do much of the feasibility work in getting a drug to switch off a receptor before the drug is even found. In my days in Galway, I would not have imagined that in a medical career, I would regularly be in contact with crystalographers. Somebody has to design a target and ask if it is drugable, if we can get a drug in there. The more sophisticated the drugs become, the less experimental we are. There is much more targeting,” Dr Giles said.

Returning to Ireland
“Returning to Ireland and contributing to Irish medicine at this level is something that is very important to me,” said Dr Giles, who is likely in the future to take up a university position based between Dublin and Galway. “In the process of doing these things, we do generate a lot of intellectual property (IP) patents. It is time for Ireland to advance to the more revenue-rich environment of generating the IP and developing the compounds themselves,” he added.