Using low doses of chemotherapy to keep cancer at bay might be more effective than trying to destroy the tumour outright, a US study has found.
The unconventional approach, which has so far only been tested in mice, suggests that some cancers could be managed as chronic diseases by adjusting the dose of chemotherapy given as treatment.
The reasoning behind this new strategy comes from similarities between Charles Darwin’s theory of evolution and how tumours grow and change. And some experts believe high-dose chemotherapy may actually make cancer harder to treat by leaving drug-resistant tumour cells room to grow.
The new ‘adaptive therapy’ strategy is designed to get around these evolutionary forces, which experts believe give rise to chemotherapy resistance.
“How cancers become resistant to treatment has been one of the greatest challenges facing doctors and their patients,” said Professor Charles Swanton, a Crick scientist part funded by Cancer Research UK.
“This work tries to find a way around a phenomenon known as ‘competitive release’ where drug resistant cancer cells survive and take over the tumour once the drug-sensitive cells have been killed off. When this happens in cancers, the disease is often much harder to treat due to the limited number of drug options available,” he added.
To test the approach, researchers from the H Lee Moffitt Cancer Centre and Research Institute in Florida in the US adjusted the dose of chemotherapy drug paclitaxel (Taxol) used to treat mice with two different kinds of breast cancer.
When given standard chemotherapy doses, their tumours initially shrank but as soon as the treatment stopped they grew back. The researchers also tried skipping doses whenever the tumour shrank, but this was also ineffective and resulted in the disease getting worse.
But using the ‘adaptive therapy’ approach – where a high initial dose was followed by progressively lower doses as the tumour responded – the mice lived longer.
In fact, the treatment was so effective that between 60 and 80 per cent of the mice could be weaned off the drug completely over an extended period of time without suffering relapses.
“This new approach is looking into how to reverse this by using different schedules of chemotherapy to keep some of the drug-sensitive cancer cells alive to out-compete the resistant untreatable cancer cells,” said Cancer Research UK’s Professor Swanton.
“Although this has work has been done in mice, it shows promise and paves the way for clinical trials with new dosing schedules in patients,” he added.
Writing in the journal Science Translational Medicine, the researchers noted that “the evolutionary principles that govern adaptive therapy may be applicable to a wide range of breast cancer treatments including hormonal manipulation and immunotherapy, although they will need to undergo further testing in those settings.”
- Enriquez-Navas, P., et al. (2016). Exploiting evolutionary principles to prolong tumor control in preclinical models of breast cancer Science Translational Medicine, 8 (327), 327-327 DOI: 10.1126/scitranslmed.aad7842