{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:53:40Z","timestamp":1762077220119,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Science Foundation","award":["ISF-1444\/18","ISF-2465\/18"],"award-info":[{"award-number":["ISF-1444\/18","ISF-2465\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Finding synergistic drug combinations is an important area of cancer research. Here, we sought to rationally design synergistic drug combinations with an inhibitor of BTK kinase, ibrutinib, which is used for the treatment of several types of leukemia. We (a) used a pooled shRNA screen to identify genes that protect cells from the drug, (b) identified protective pathways via bioinformatics analysis of these gene sets, and (c) identified drugs that inhibit these pathways. Based on this analysis, we established that inhibitors of proteasome and mTORC1 could synergize with ibrutinib both in vitro and in vivo. We suggest that FDA-approved inhibitors of these pathways could be effectively combined with ibrutinib for the treatment of chronic lymphocytic leukemia (CLL).<\/jats:p>","DOI":"10.3390\/cells11223671","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:11:21Z","timestamp":1669000281000},"page":"3671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Search for Synergistic Drug Combinations to Treat Chronic Lymphocytic Leukemia"],"prefix":"10.3390","volume":"11","author":[{"given":"Eleonora Ela","family":"Hezkiy","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1744-337X","authenticated-orcid":false,"given":"Santosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valid","family":"Gahramanov","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Yaglom","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-5469","authenticated-orcid":false,"given":"Arkadi","family":"Hesin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6565-8335","authenticated-orcid":false,"given":"Suchita Suryakant","family":"Jadhav","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Guzev","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0906-2841","authenticated-orcid":false,"given":"Shivani","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-9197","authenticated-orcid":false,"given":"Elena","family":"Avinery","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8430-0486","authenticated-orcid":false,"given":"Michael A.","family":"Firer","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Ariel University, Ariel 40700, Israel"},{"name":"Adelson School of Medicine, Ariel University, Ariel 40700, Israel"},{"name":"Ariel Center for Applied Cancer Research, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-320X","authenticated-orcid":false,"given":"Michael Y.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Ariel University, Ariel 40700, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vaisitti, T., Arruga, F., and Ferrajoli, A. 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