Imma Perfetto
Cosmos science journalist
Researchers have detailed the 4 common ways cancers can become less susceptible to the drugs used to treat them.
They say it could help tackle drug-resistant cancer and identify new targets for drug development.
The new research is detailed in a Nature Genetics study.
“Before this it has been difficult to get a large-scale understanding of why and how drug resistance in cancer develops,” says Dr Mathew Garnett, senior author of the study from the Wellcome Sanger Institute and Open Targets, UK.
Drug resistance is frequently caused by mutations in cancer cells’ genes, which make them less responsive over time. Treatments after this happens are known as second line therapies, but options for these can be limited.
“This research brings us one step closer to being able to match combination or second-line therapies to a person’s genetic makeup, to try and ensure that treatments are as effective and personalised as possible,” says Garnett.
The team used CRISPR gene editing and other genomic techniques to create a map of drug resistance mutations in colon, lung, and Ewing sarcoma cancers, which are prone to developing drug resistance and have limited available second line treatments.
“Having a rapid way to identify these mutations in patients and understand how to combat them is key to treating cancer,” says first author of the study Dr Matthew Coelho, also from the Wellcome Sanger Institute and Open Targets.
“Our study details how mutations fall into four different groups, which might need different treatment plans,” says Coelho.
These categories include:
- Canonical drug resistance mutations, which lead to the drug being less effective.
- Drug addiction mutations, in which cancer cells use the drug to help them grow, instead of destroying them.
- Driver mutations, which allow cancer cells to use a different pathway to grow, avoiding the pathway the drug may have blocked.
- And drug sensitising variants, which make the cancer more sensitive to certain treatments and may indicate a patient would benefit from particular drugs.
“For example, if there are drug addiction mutations, taking a break from treatment may help,” says Coelho.
“By using cutting-edge genetic techniques, we have started to build a large-scale and rapid way to understand drug resistance and hopefully find new targets for second-line treatments.”
The new research is detailed in a Nature Genetics study.
