Cancer treatment

With almost half a million people in Germany expected to fall prey to cancer this year, some 1,800 of them under the age of 15, scientists at Berlin's Charité hospital are working on a new form of treatment. They hope it will help transform cancer into a chronic rather than a fatal illness.

They are beginning to understand that each tumor -- an accumulation of genetic mutations -- has its own genetic makeup. And as Reinhold Schafer, deputy director of the Charité Comprehensive Cancer Center in Berlin explained, in keeping with that discovery, they are now working on personalized approach for individual patients.

"We are beginning to understand that a cancer genome carries many more mutations than we would have anticipated," he told Deutsche Welle. "So far we are dealing with a handful of mutations, so called driver mutations, which drive the onset and are also responsible for the maintenance of the cancer phenotype."

Impotent Mix

As things stand, cancer patients can expect to be treated with a concoction of different and expensive drugs, some of which will have absolutely no effect on certain tumors, but which will do serious harm to other tissues in a given patient's body.

That is where genome sequencing technology comes in. As it becomes less expensive and more accessible, the potential for an individualized approach to cancer treatment is becoming a reality. And that is good news for Schafer and his colleagues on the Treat1000 project, which plans to do as its name suggests.

"The idea is to use deep sequencing technology to comprehensively assess the cancer genomes of these thousand patients and to compare the cancer genomes with a constitutive situation in order to find out which are the cancer-specific molecular alterations in these patients."

Conventional cancer medicine has focused on driver mutations, which are a kind of common denominator between cancers of the same type. Schafer, however, is exploring "passenger mutations," which are unique to each patient.

"There's a bunch - hundreds, thousands - of mutations that occur in cancer patients, and so far we don't have any idea what they are doing at the functional level, but they are there."

Bar code for cancer

The researcher describes the combination of passenger mutations as an "individual bar code" for cancer. As personalized treatment becomes more advanced, oncologists will be able to target specific mutations with combinations of drugs they know have a high probability of working.

Hans Lehrach, head of Vertebrate Genomics at the Max Planck Institute for Molecular Genetics in Berlin, says using computer modeling makes it possible to sort through thousands of drug candidates in search of a combination which can combat a tumor while minimizing damage to a patients' overall health.

The procedure requires researchers to take DNA samples from patients' blood and tumor and decode the genetic information of both.

"We can combine that with the results from decades of cancer research which has given us a very large amount of information on the pathways which connect the different components we see in the sequencing," Lehrach told Deutsche Welle.

Scientific evolution

Improvements in genome sequencing technology have made Treat1000 a viable project. It currently takes Lehrach and his team about 10 days to sequence a human genome. By comparison, the original Human Genome Project took from 1990 to 2003 to first identify and sequence human DNA. But both science and technology have moved on since then.

"We can try the wrong treatment thousands of times on the computer model but before we go to the patient we should be very sure that whatever we do will help the patient, it will not have any unacceptable side effects," Lehrach said.

Lehrach hopes an individualized approach to cancer treatment would enable doctors to respond to changes in tumors and better control them. But personalized medicine doesn't only have the potential to change the fates of cancer patients, it is also likely to drastically change the way clinical trials of drugs are conducted.

More personal all-round

Clinical trials aren't currently stratified by the genetic profiles of their participants. Patients suffering from the same tumor all receive identical treatments, a practice which may have caused research on some drugs to be discontinued on account of their apparently low rate of effectiveness.

However those drugs may be highly effective if tested on a subset of patients who share similarities in their 'bar code' of passenger mutations. And that, says Schafer, means the cancer battle of the future will become about tailoring treatments to the genetic profiles of individual patients.

"Some people even believe it's the big revolution in medicine, but time will tell," Schafer said. "I guess it's more or less a series of little revolutions, little progress, but steady progress. Hopefully."

Reporter: Gerhard Schneibel (tkw)
Editor: Jennifer Abramsohn