Excerpts from genengnews.com/topics/omics...
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Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has remarkable efficacy in most patients with CLL. It is becoming the standard of care for most patients requiring treatment due to its clinical efficacy and mostly tolerable side effects. However, it does not cure the disease, and patients must undergo prolonged periods of treatment.
According to Bock’s team at CeMM, CLL cells and other immune cells that respond to Ibrutinib manifest distinctive epigenetic and transcriptional patterns. These patterns predict how swiftly the treatment is having an effect on the CLL cells and how long it takes for the disease to respond in each individual patient.
In previous studies, scientists had investigated only specific aspects of the molecular response to ibrutinib, focusing largely on genetic drug resistance or the transcriptome response of cancer cells. In the current study, CeMM researchers tried a new, more comprehensive approach. They conducted a genome-scale, time-resolved analysis of the regulatory response to this drug in primary patient samples.
The scientists simultaneously monitored the activity, regulation, and expression of the CLL cells and other cell types of the immune system. Importantly, they performed this analysis at eight predefined time points during the ibrutinib therapy, following seven individual patients over a standardized 240-day period after the start of the treatment.
After the CeMM team amassed a dataset, they put it through integrative bioinformatic analysis to generate one of the first high-resolution, multi-omics time series of the molecular response to targeted therapy in cancer patients. This work, the CeMM team asserts, establishes a broadly applicable approach for analyzing drug-induced regulatory programs, identifying molecular response markers for targeted therapy.
These results will help develop personalized strategies for managing CLL as a chronic disease, which is particularly relevant for CLL as a disease of the elderly. Also, they will help stratify patients into fast and slow responders based on characteristic molecular markers and open new directions for the development of ibrutinib-based combination therapies for CLL.
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The CeMM study is published in Nature nature.com/articles/s41467-...