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The future of cancer treatment?

9th July 2012

Researchers in the United States have used genetic sequencing to treat a colleague suffering from the very disease he was studying.

DNA

Lukas Wartman developed adult acute lymphoblastic leukaemia while working at Washington University, which is at the cutting edge of research into the human genome.

His condition was rapidly worsening, and no treatment was available, so his research colleagues used one of the university's genome sequencing machines and a supercomputer to examine his entire genome, normal and abnormal, as well as his RNA.

Led by Timothy Ley, associate director of the university’s genome institute, the team only had one chance to try to find a treatment that worked for Wartman.

The team fully sequenced the genes of both his cancer cells and his healthy cells in order to compare them, and looked at his RNA, which is chemically similar to DNA.

While they identified a number of genes that were functioning abnormally, no treatments were currently available that would target them. Instead, using a clue from Wartman's RNA, they identified a normal gene that was pumping out large amounts of a protein believed to be fuelling the cancer.

There was already a drug in existence that targeted this gene, but it was currently licenced for use in kidney cancer.

Moreover, it cost around US$300 a day. Wartman funded some of the drug purchase himself, while his colleagues held a whip-round for more supplies, giving him a month's supply in total.

The hope was that the new drug, known as sunitinib or Sutent, would shut down the malfunctioning gene.

The treatment appeared to work, at least for the time being, because Wartman's cancer has been in remission since last autumn.

Researchers say the approach may herald a breakthrough in cancer treatment, which has previously focused on the organs affected by a cancer, whether they be liver, brain, bone marrow, blood or colon.

But Wartman's experience suggests that it is genes that drive a cancer from the outset.

The same genes can drive cancers in totally different body parts, and even cancers of the same part may have different genetic origins.

Future treatments are likely to be tailored to the specific gene mutations affecting an individual tumour, using drugs that target one or more mutated genes.

The approach could be analogous to the cocktails of medicines used in the treatment of HIV.

Wartman is not the first cancer patient to have used whole genome sequencing, but the technique is currently very expensive and not including in most healthcare insurance plans.

Steve Jobs paid US$100,000 to have his genome sequenced after he had run out of options to treat his pancreatic cancer.

And journalist Christopher Hitchens asked the National Institutes of Health for advice about getting his oesophageal cancer analysed genetically. Neither worked, however, possibly because the analysis of genetic sequences is a highly skilled task which is still in its infancy.

That could change within the next few years, however, with medical experts predicting that genetic analyses of cancers will become routine.

Ley said it was crucial to understand the genetic background to a patient's cancer, otherwise doctors were operating blindly without a map of the terrain.

Ley said his team would now focus on building that map.

Big pharmaceutical companies and biotechnology firms alike are already beginning to test drugs that target genes rather than tumours.

According to Heidi Rehm, who heads the molecular medicine laboratory at Harvard’s Partners Healthcare Center for Personalised Genetic Medicine, Harvard Medical School expects eventually to offer whole genome sequencing to help cancer patients identify treatments.

But the operations that were performed on Wartman's sequencing were at a whole new level of complexity, Rehm warned.

Wartman's remission came after he was enrolled by his colleagues in a research study, meaning that his genetic analysis was paid for by the university and research grants.

 

 

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