r/Biochemistry • u/jargs92 • 6h ago
Research Imatinib resistance as an example of cancer evolution: connecting a protein change to clonal selection
I made a 13-minute introduction to cancer evolution, and the imatinib section may be of interest here. It connects a molecular change in a drug target with selection among cancer-cell populations.
In Gorre et al. (2001), resistance was associated with a threonine-to-isoleucine substitution in the ABL kinase domain in six of nine patients; the other three showed BCR-ABL amplification. So the example involves both altered drug-target interaction and increased gene copy number, rather than one universal resistance mechanism.
Original paper: https://pubmed.ncbi.nlm.nih.gov/11423618/
The imatinib section starts at 8:55. The broader video uses melanoma to introduce clonal diversity and then discusses TRACERx and experimental adaptive therapy. I'm a genetics PhD at UCL studying cancer evolution; the video description includes references and corrections to the simplified narration.
