Cancer is often said to be not one disease, but many. Each person’s tumour has a different set of mutations, so while a certain treatment might see off one person’s breast cancer, for instance, it may fail at treating someone else’s.
The hard part is knowing which treatment will be the best for a specific tumour. Now doctors are starting to determine the best options by testing different drugs on specially created animals that have been given replicas of a patient’s cancer – known as “cancer avatars”.
One option could be to generate Drosophila fruit flies with the same genetic mutations as a person’s cancer. These flies are small and live only for a short time, meaning researchers can generate large numbers of them in multiple rows of test tubes. Robotic equipment can then be used to screen hundreds of drug combinations on the flies.
This approach was used to guide treatment for a man who had terminal colon cancer. He died after about three years but this was probably longer than he would have lived otherwise, says Ross Cagan of the Icahn School of Medicine at Mount Sinai in New York.
Before making the fruit fly avatars, the man’s cancer had already spread round his body and developed resistance to several drugs. Genetic sequencing revealed the tumour had at least nine cancerous mutations. The team genetically engineered a strain of flies that had all these mutations in their gut cells – and then bred over 300,000 of them.
They then developed a robotic system to feed the flies and test different medicines on them. In this way, they screened 121 existing medicines – including both cancer drugs or treatments for other conditions – either singly or in combinations of up to three.
Several combinations stopped the flies from dying and slowed the growth of their gut tumours. The doctors eventually settled on a cancer drug called trametinib and an osteoporosis treatment called zoledronate, which had the best combination of effectiveness and predicted safety, and gave these to the man.
Animal avatars are needed, says Cagan, because although we already have some cancer medicines designed to combat individual mutations, we can’t yet predict how a tumour with multiple altered genes will respond. “We don’t yet know the best drug combinations for someone with nine tumour mutations.”
The approach isn’t a cure, though. The man stopped responding to this treatment after 11 months. The team sequenced the DNA of tumour cells in his blood and could not identify the mutations that had made it resistant to the new treatment.
Mouse avatars are a more widespread approach. These are being developed at several universities, and a US firm, Champions Oncology, already offers this testing service to people with cancer. When a person has a tumour removed, a small piece is sent to the firm, which then implants cells from it into a small number of mice. A few months later, the results from drug-testing in mice are sent back to the person’s doctors.
Flies, however, are particularly amenable to robotic screening methods, and may also be preferable for those concerned about the ethics of animal research. The disadvantage, however, is that they are so different to humans, having an extremely simple immune system, for instance.
But all the different models have their pros and cons, says Rita Fior of the Champalimaud Centre for the Unknown in Lisbon, Portugal, who is developing zebrafish avatars. No large-scale trial has yet shown that any of these approaches leads to people living longer than if their doctors just used their best judgement.
“Our goal is to predict in advance what’s the best treatment and get the right drug the first time,” says Fior. “Then we can stop experimenting on patients.”
Journal reference: Science Advances, DOI: 10.1126/sciadv.aav6528 More on these topics:
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