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Letters to the Editor
reached after a cardioprotective 500 mg/m2 dose (36.5 mg/mL or 135 mM).14 This suggests that DXZ could be repurposed as a TOP2-targeting anti-MM agent as part of a combinatorial approach, however its posology is not well suited to recurrent or chronic administration. We are unaware of any other selective small-molecule TOP2B inhibitors. Greater understanding of the struc- ture-activity relationship between DXZ and TOP2B may allow the rational development of related chemotypes for drug therapy. Further investigation of these mechanisms by which TOP2B inhibition leads to anti-MM activity could reveal alternative pathways to IMiD potentiation.
Matteo Costacurta,1,2 Stephin J Vervoort,1,2 Simon J Hogg,1,2
Benjamin P Martin,1,2 Ricky W Johnstone1,2# and Jake Shortt1,2,3,4#
1Translational Hematology Program, Peter MacCallum Cancer Center, Melbourne; 2Peter MacCallum Department of Oncology,
The University of Melbourne, Parkville, Melbourne; 3Monash Hematology, Monash Health, Clayton, Melbourne and 4Blood Cancer Therapeutics Laboratory, School of Clinical Sciences at Monash Health, Monash University, Clayton, Melbourne, Victoria, Australia.
#RWJ and JS contrituted equally as co-senior authors.
Correspondence:
RICKY W. JOHNSTONE - ricky.johnstone@petermac.org JAKE SHORTT - jake.shortt@monash.edu doi:10.3324/haematol.2020.265611
Received: July 3, 2020.
Accepted: December 22, 2020. Pre-published: December 30, 2020.
Disclosures: JS sits on advisory boards and received speakers fees from Celgene and BMS outside of the published work; The Johnstone laboratory receives funding support from Roche, BMS, Astra Zeneca, and MecRx; RWJ is a paid scientific consultant and shareholder in MecRx; all other authors declare no conflicts of interest.
Contributions: MC conducted experimental work, planned experi- ments, analyzed the data and wrote the manuscript; SV helped with experimental planning, analyzed sequencing data and contributed with manuscript writing; SH analyzed sequencing data; BM helped with screening experiments; RJ and JS supervised the project, planned experiments and wrote the manuscript.
Funding: JS is supported by an Australian Medical Research Future Fund Next Generation Clinician Researcher Fellowship; this research was funded by NHMRC project Ggrant 1127387; RWJ was sup- ported by the Cancer Council Victoria, National Health and Medical Research Council of Australia (NHMRC), and The Kids’ Cancer Project; The Victorian Center for Functional Gnomics, the Molecular Genomics Core and the Flow Cytometry Core Facilities at the Peter
MacCallum Cancer Center provided excellent technical support; The Peter MacCallum Foundation and Australian Cancer Research Foundation provide generous support for equipment and core facilities.
Acknowledgments: We acknowledge the FACS facility and the Molecular Genomic Core at the Peter MacCallum Cancer Center for contributing to this work.
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