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Updated: Dec 26, 2025

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
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Aurora B kinase as a therapeutic target in acute lymphoblastic leukemia

Hiroaki Goto1, Yuki Yoshino2, Mieko Ito2

  • 1Division of Hematology/Oncology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa Minami-Ku, Yokohama, Japan. hgotou@kcmc.jp.

Cancer Chemotherapy and Pharmacology
|March 8, 2020
PubMed
Abstract

Insights

Novel drug screening identified barasertib-HQPA as a promising agent for acute lymphoblastic leukemia (ALL). Aurora B kinase is a key target, suggesting combination therapies could improve outcomes for relapsed or refractory ALL patients.

Area of Science:

  • Hematology
  • Oncology
  • Pharmacology

Background:

  • Acute lymphoblastic leukemia (ALL) remains a significant challenge, particularly in relapsed or refractory cases, necessitating novel therapeutic strategies.
  • Standard chemotherapy, while effective, has limitations, driving the search for targeted agents.
  • In vitro drug screening provides a platform for identifying new molecularly targeted therapies.

Purpose of the Study:

  • To identify active molecular targeting agents against acute lymphoblastic leukemia (ALL) using an in vitro drug screening system.
  • To evaluate the efficacy of various agents across a diverse panel of ALL cell lines and clinical samples.
  • To explore potential drug combinations for enhanced therapeutic effects.

Main Methods:

  • Screened 81 agents for cytotoxicity against 22 ALL cell lines and clinical samples using in vitro drug sensitivity tests.
  • Calculated drug effect score (DES) to quantify drug efficacy and enable comparisons.
  • Assessed drug combination effects using the Bliss independent model and validated with the improved isobologram method.

Main Results:

  • Barasertib-HQPA (active metabolite of barasertib, an aurora B kinase inhibitor), alisertib (aurora A kinase inhibitor), and YM155 (survivin inhibitor) demonstrated broad efficacy against ALL cells.
  • Barasertib-HQPA showed significantly higher DES in ALL clinical samples compared to controls.
  • Barasertib-HQPA exhibited additive to synergistic effects when combined with eribulin.

Conclusions:

  • Aurora B kinase is a validated therapeutic target in a wide spectrum of ALL.
  • Combination therapy involving barasertib and microtubule-targeting drugs warrants further clinical investigation for ALL treatment.
Keywords:
Acute lymphoblastic leukemiaAurora B kinaseBarasertibIn vitro drug sensitivity testSurvivin

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