Abstract
Accelerating cancer evolution: a dark side of SIRT1 in genome maintenance
Highlights
One important aim in cancer treatment is to kill cancer cells to control tumor growth and achieve remission
The authors showed that the role of SIRT1 in promoting mutation acquisition is associated with its ability to enhance aberrant DNA damage repair, in particular, the error-prone non-homologous end joining (NHEJ) repair
The findings by Wang et al apparently contrast with previous reports that SIRT1 maintains genome integrity [6, 7], which would predict that loss of SIRT1 could increase genetic instability and mutagenesis
Summary
One important aim in cancer treatment is to kill cancer cells to control tumor growth and achieve remission. Wang et al showed that mammalian stress response gene SIRT1 is a key player promoting acquisition of genetic mutations for CML drug resistance [2]. SIRT1 inhibition by small molecule inhibitors or gene knockdown blocks de novo acquisition of BCR-ABL mutations in blast crisis CML cells and prevents CML cell relapse from imatinib treatment.
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