Systems biology drug screening identifies statins as enhancers of current therapies in chronic lymphocytic leukemia.

ABSTRACT: Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. We used a platform for drug discovery based on systems biology and artificial intelligence, to identify drugs targeting key proteins described to have a role in the microenvironment. The selected compounds were screened in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested co

SUBMITTER: Gimenez N 

PROVIDER: S-EPMC7746765 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature