"Resistance to treatment is arguably the major issue facing patients with advanced cancers, for whom even effective treatments ultimately fail. We have uncovered a fundamental survival strategy that cancer cells use to develop resistance, which has given us new possible therapeutic strategies."
Professor David Thomas - Director, The Kinghorn Cancer Centre
- Read more about the scientific breakthrough below.
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"We discovered that when cancer cells are exposed to targeted therapies, they undergo a process called ‘stress-induced mutagenesis’ – they generate random genetic variation at a much higher rate than cancer cells not exposed to drugs. The stress-induced mutagenesis process is ancient – single celled organisms like bacteria use the same process to evolve when they encounter stress in their environment.”
Dr Arcadi Cipponi, Senior Research Officer - Genomic Cancer Medicine Lab
Understanding how cancer cells evolve and mutate will help us to stop treatment resistance and change millions of lives.
The full story: 7 years and 240 experiments
Seven years ago, Dr Cipponi’s team launched a mission to investigate the processes that allow cancer cells to elude previously effective therapies.
The team analysed biopsy samples from cancer patients before and after they were treated with targeted therapies.
When the researchers looked at how cancer cells behaved, they discovered something surprising – the cancer cells from patients that had received targeted therapies showed much higher levels of DNA damage than pre-treatment samples.
Under stress from the treatment, the cells in a broad range of cancers (including sarcomas, melanoma, breast and pancreatic cancer) began to make deliberate mistakes as they copied their DNA. The process, called ‘stress-induced mutagenesis’, eventually enabled these cells to survive and resist the drug treatment.
As Dr Cipponi describes it, it’s an ancient process we’ve witnessed before in bacteria that develop resistance to antibiotics. But this is the first time we’ve ever been able to link the same behaviour to cancer cells.
Do we have a treatment for this?
Dr Cipponi’s research shows that treatments to treat cancer without causing stress-induced mutagenesis not only exist, but they could work.
The team tested an experimental model of pancreatic cancer, a cancer with one of the highest mortality rates (around 91%).
They found that when they combined a cancer treatment (palbociclib) with rucaparib, a drug that selectively targets cells with impaired DNA repair, they could reduce cancer growth by almost 60% in only 30 days, compared with the cancer drug alone.
Rucaparib is part of a class of drugs called PARP inhibitors and they are already approved for use in people, so these findings will be able to help patients that much faster.
Thanks to these results, the team is working tirelessly to translate this discovery into real clinical benefits for people living with cancer.