Histone proteins are the principal components of chromatin and chromosomes, help compact the DNA, and participate in regulation of gene expression that determines a cell’s function. Chemical modifications of histones, such as acetylation and methylation, are a mechanism by which histones exert their regulatory effect on gene expression. Histone modification levels differ between different cell types. For example, embryonic stem cells generally have higher levels of histone acetylation than more differentiated cells for reasons that are unclear but are under investigation. Cancer cells also show variability in the levels of histone modifications. We had previously found that the levels of histone modifications in cancer tissues can distinguish indolent versus aggressive forms of cancer. This information could be useful in determining the correct treatment plan for individual patients.

In this collaborative study, we show that histone modifications can also distinguish the aggressive forms of pancreatic cancer from the ones that are less so. But more important, histone modifications can predict the response of patients to 5-fluorouracil (5-FU), a chemotherapeutic agent that is commonly used to treat cancer patients. This is the first time that histone modifications have been shown to be predictive of drug response. Therefore, histone modifications levels may help identify cancer patients’ responsiveness to 5-FU, enabling the physician to make better informed clinical decisions. While promising, our data need to be validated independently by other laboratories to verify the conclusions.