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878228.pdf (2.67 MB)

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2020-12-17

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cc-by (c) Gimenez, Neus et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223852

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

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Recurs relacionat

https://doi.org/10.1038/s41598-020-78315-0

Resum

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 compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. We proposed that systems biology approaches combined with pharmacological screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells.

Matèries

Models moleculars, Estatines (Medicaments cardiovasculars), Medicaments, Leucèmia limfocítica crònica, Marcadors bioquímics

Matèries (anglès)

Molecular models, Statins (Cardiovascular agents), Drugs, Chronic lymphocytic leukemia, Biochemical markers

Citació

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Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

GIMENEZ, Neus, TRIPATHI, Rupal, GIRÓ, Ariadna, ROSICH, Laia, LÓPEZ GUERRA, Mónica, LÓPEZ OREJA, Irene, PLAYA-ALBINYANA, Heribert, ARENAS RÍOS, Fabián, MAS, José manuel, PÉREZ GALÁN, Patricia, DELGADO, Julio (delgado gonzález), CAMPO GÜERRI, Elias, FARRÉS, Judith, COLOMER PUJOL, Dolors. Systems biology drug screening identifies statins as enhancers of current therapies in chronic lymphocytic leukemia. _Scientific Reports_. 2020. Vol. 10, núm. 1. [consulta: 5 de gener de 2026]. ISSN: 2045-2322. [Disponible a: https://hdl.handle.net/2445/223852]

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