Researchers at City St George’s, University of London say cancer outcomes might improve if doctors switch to a new therapy while a tumor is still shrinking, rather than waiting for clear signs the disease is growing again. In mathematical models grounded in evolutionary theory, the team found that carefully timed switches—potentially involving three or more treatments—could reduce the odds that resistant cancer cells drive relapse. Three small clinical trials in soft-tissue cancer, prostate cancer and breast cancer are already testing variations of the idea.
Smarter timing may be one of the keys to making cancer treatment more effective, according to a new study led by Dr. Robert Noble, a senior lecturer in the Department of Mathematics at City St George’s, University of London.
The researchers argue that, instead of continuing a therapy until scans or tests show the cancer is growing again, clinicians could consider switching to another treatment while the tumor is still responding. The aim is to limit the time resistant cancer cells have to expand and accumulate additional mutations that might also protect them from later therapies.
“Although tumors may at first shrink under therapy, in many cases they eventually regrow,” Noble said, attributing many relapses to a small number of cells that survive treatment because they carry resistance mutations.
To explore the idea, Noble and colleagues used mathematical models adapted from tools used to study evolution under changing environmental pressures. In their framework, each therapy acts as a new “pressure” on the tumor: susceptible cells are killed off, while any cells with mutations that confer resistance are more likely to survive and multiply.
The models suggest that switching treatments before a visible relapse could generally perform better than the usual approach of waiting until the cancer begins growing again. The study also suggests that a sequence of two treatments—even if timed optimally—may be most likely to succeed only when tumors are relatively small. For larger tumors, the authors argue that switching between three or more treatments could make it harder for a single resistant population to dominate.
The findings are based on modeling rather than direct patient outcomes, and the researchers said more laboratory work and clinical studies will be needed to determine whether early switching is safe and how best to time any changes in therapy.
The research article is published in the journal Genetics.
