Dr Robert Noble, Senior Lecturer, Department of Mathematics, led the study based on modelling from evolutionary theory.
A new study provides hope that smarter timing of cancer treatments could improve cure rates.
Using modelling from evolutionary theory, the study predicts that targeting small tumours with a second treatment while the cancer is responding to the first, should generally outperform standard care.
The study came about when Principal Investigator, Dr Robert Noble, Senior Lecturer at the Department of Mathematics, City, St George’s, University of London, sought to tackle a major problem in cancer care.
“Although tumours may at first shrink under therapy,” he explains, “in many cases they eventually regrow. These relapses stem from a small number of cancer cells that have gained mutations making the cells resistant to the treatment.”
The standard clinical approach is to wait and see if a tumour regrows before trying a different treatment. By this point, some tumour cells are likely to have gained mutations making them resistant to the second treatment, which then also fails.
Evolutionary theory suggests an alternative strategy. Instead of waiting, it might be better to switch to a second treatment while the tumour is still responding to the first one. This “kick it while it’s down” approach is most appropriate when doctors know from experience that even the best option for a first treatment often fails due to resistance.
As Dr Noble explains in a podcast about the study, “Evolutionary approaches have been very successful in other contexts, such as combatting antibiotic resistance, or predicting what vaccines we should use in a particular flu season. There is every reason to suppose that similar approaches should work in tumours.”
To test this hypothesis, Dr Noble and colleagues adapted mathematical methods more commonly used to understand how plants and animals evolve in response to environmental pressures, such as climate change.
In their study, the team concludes that their findings justify further experimental and clinical testing of this innovative evolutionary treatment strategy. Three small clinical trials are already underway in soft-tissue cancer, prostate cancer, and breast cancer. Further trials are in development.
“Our models predict that this new approach will generally outperform the standard of care,” explains Dr Noble. “A sequence of two treatments, even if optimally timed, is likely to succeed only in relatively small tumours. But we have reason to hope that switching between three or more treatments, following the same principle, could eliminate larger tumours.”
The full research article is published in the journal Genetics.
Research Team
Dr Noble conducted this research with an international team of mathematical biologists. The work grew out of the final-year project of Srishti Patil, a master’s student at the Indian Institute of Science Education and Research, Pune, who spent some months at City St George’s, University of London under Dr Noble’s supervision. The team also included Johns Hopkins University undergraduate Armaan Ahmed and Dr Noble’s long-term collaborator Dr Yannick Viossat of Université Paris Dauphine-PSL.
Genetics Society of America Podcast
The story behind the paper is told in an associated podcast recorded by the Genetics Society of America.
Find out more
Further details of Dr Noble’s research are available on his website