Search for Synergistic Drug Combinations to Treat Chronic Lymphocytic Leukemia

Eleonora Ela Hezkiy, Santosh Kumar, Valid Gahramanov, Julia Yaglom, Arkadi Hesin, Suchita Suryakant Jadhav, Ekaterina Guzev, Shivani Patel, Elena Avinery, Michael A. Firer, Michael Y. Sherman

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish
Article number3671
JournalCells
Volume11
Issue number22
DOIs
StatePublished - Nov 2022

Keywords

  • CLL
  • bortezomib
  • drug combination
  • ibrutinib
  • rapamycin
  • synergy
  • xenograft

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Search for Synergistic Drug Combinations to Treat Chronic Lymphocytic Leukemia'. Together they form a unique fingerprint.

Cite this