Zebrafish could be key to bespoke cancer therapies
Cancer patients could be given living "avatars" to enable doctors to test different kinds of drugs to find an effective treatment.
Researchers in Portugal said they had demonstrated for the first time that zebrafish larvae could be used as a host for samples of an individual's tumour. This would allow doctors to try different drugs to develop a personalised course of treatment.
One problem with cancer is everyone has their own unique type and tumours can react in different ways to drugs. Cancer cells can even evolve over time. But there is great hope that personalised medicine will lead to a revolution in treatment by providing a solution to this problem. Previously mice, which as fellow mammals are closer to humans than fish, have been used as a model in this way, but tumours can take months to grow inside them. Preliminary results of the new study suggested zebrafish larvae can also be used as a living model, enabling doctors to get results within two weeks.
Dr Miguel Godinho Ferreira, of the Champalimaud Centre for the Unknown in Lisbon, Portugal, said: "We demonstrated for the first time that zebrafish and mice react to treatments in the same way: with the same drugs, we obtain the same results in mice and in zebrafish larvae."
"My main concern has been, for a long time, the fact that tumours change. In some cases, the efficacy rate of chemotherapies can be low, sometimes around 35 per cent. This means that some patients risk taking inadequate drugs that weaken them and without a proper test, there is no way to know who will benefit and who won't," he added.
Dr Rita Fior, who also worked on the study, said she had been "very frustrated about the fact that although we have so much technology ... if someone has a tumor we still don't know which drug is best for that specific tumour, within the several approved therapeutic options".
When the researchers investigated the potential of zebrafish larvae to be used as a host for human cancers they found it enabled them to consider changes down to a single variant of an individual gene. Dr Godinho Ferreira described this as "incredible resolution power". They then tested this power by obtaining tumour samples from five patients being treated in hospital and subjecting them to the same chemotherapy given to the humans in their zebrafish larvae avatars. This is the normal course of treatment surgery, followed by chemotherapy to prevent the cancer coming back.
"For two of the patients, the tumours transplanted into the larvae did not respond to the chosen chemotherapy," Dr Fior said. "And in fact, consistent with our results, a short time afterwards those patients relapsed." Two other patients whose fish avatars responded to the treatment were "still doing well as far as we know", Dr Godinho Ferreira added.
So the avatars appear to have correctly predicted what would happen in four out of the five cases. However, this is too small a sample from which to draw a significant conclusion and the researchers' next step is to compare the results of hundreds of human and avatar cases, which could take about two years. "If everything goes well, we will be able to inform oncologists on the result of the different therapies in the avatars; they will always have the final word in terms of deciding which therapy to choose, but they will be able to base themselves on individual tests," Dr Godinho Ferreira said.
"Our dream is to develop an antibiogram' for cancer. Just as we currently do this today for bacterial infections, we hope to obtain a kind of matrix for each patient of the efficacy of the various drugs that will allow physicians to choose the most indicated therapy for each person."
The study was described in a paper in the journal Proceedings of the National Academy of Sciences.