Scientists develop new directory to aid cancer treatment

Scientists develop new directory to aid cancer treatment

6 October 2009

Scientists investigating how drug combinations affect cancer-causing genes have developed a new directory to help doctors identify effective treatment sooner and help save lives. The directory lists some of the thousands of genes that could be responsible for causing cancer, and shows the effects that combinations of three cancer-fighting drugs have on them.
 
Already the electronic directory, developed by researchers at St George’s, University of London, has helped identify how some solid cancers, including pancreatic cancer, may be treated by medication earlier than currently thought possible.
 
Thalidomide and lenalidomide are two leading cancer-fighting drugs whose effects are analysed in the directory. These can be used separately or together to target and manipulate genes to prevent, and even reverse, the growth of cancer cells. Despite its controversial past, thalidomide is now recognised for its cancer-fighting properties and both these drugs are currently used to treat multiple myeloma, more commonly known as bone marrow cancer.
 
The directory displays the effects of the drugs as a spreadsheet that can be searched by drug type and or gene name. It also shows the effects of a less common cancer-fighting drug, pomalidomide, which can be combined with other drugs to enhance treatment.
 
These drugs work by neutralising the cancerous substances produced by the mutated genes suspected of causing the cancer cells to grow.
 
“The principle behind gene therapy is that by inserting new copies of a particular gene into human cells, it should be possible to correct defects or to enhance beneficial biological processes, in order to treat certain diseases,” explains the lead author of the directory, Dr Wai Liu from St George’s. “This can be done with specialised viruses that can be engineered to carry a human gene, which is then introduced into the defective cancer cells.”

One of the reasons drug therapy doesn’t always work as quickly as hoped is because, despite many medical advances, there are still knowledge gaps around how different drugs affect different genes in patients. “The doctor makes an assessment as to which of the thousands of genes is the root cause of the cancer, and then he or she prescribes drugs which will target that gene. But our understanding of how drugs affect different genes in patients is incomplete, which means that doctors can’t always get it right first time,” explains Dr Liu.

“This directory pinpoints the effects each of the three drugs has on patients and provides a guide for medics to help them identify the most effective treatment,” he continues.

It identifies the effects of the drugs when used in isolation and goes on to predict what they would be when used together in drug combination treatment.
 
“Combining drugs can often increase the effectiveness of treatment,” explains Dr Liu, “mainly because the body is less able to build up a resistance.”

The impact of the drugs can be viewed by their effect on each individual gene, as well by the wider effects they would have on other genes in the body.

Dr Liu, working with Professor Angus Dalgleish, also from St George’s, compiled the directory from studies that tested the drugs’ effects on cancerous cells in lab-based tests. They also tested their effect on tumours in mice. The team then used highly sophisticated ‘gene chip’ technology to simultaneously detect changes in more than 40,000 genes in cells treated with each of the three drugs individually.

Using the directory, researchers have already identified a drug combination that could help to treat solid cancers, such as cancer of the pancreas, that are sometimes caused by a mutation within a particular group of genes - known to medics as the ‘notch signalling’ pathway. The notch genes are rapidly becoming a focus for research as they are responsible for a number of crucial stages in the development of cancer. By neutralising the effects of these genes, cancer growth could be halted in their track.

Dr Liu explains: “Doctors are already prescribing patients with drug combinations that include thalidomide and lenalidomide to fight solid cancers, and these have shown good success rates. This breakthrough analyses allows doctors to design new methods of treatments that may be effective against cancers that develop from mutations in a group of cancer-causing genes which is renowned for being difficult to target with drugs.

“It is hoped that this directory can help medics identify a number of similar treatment breakthroughs,” concludes Dr Liu.

The directory is a result of a research project entitled ‘A microarray study of altered gene expression in colorectal cancer cells after treatment with immunomodulatory drugs: differences in action in vivo and in vitro’. This is published in the Molecular Biology Reports journal and is available on the pubmed website.