Targeting the Retinoblastoma/E2F repressive complex by CDK4/6 inhibitors amplifies oncolytic potency of an oncolytic adenovirus

Jana Koch; Sebastian J. Schober; Sruthi V. Hindupur; Caroline Schöning; Florian G. Klein; Klaus Mantwill; Maximilian Ehrenfeld; Ulrike Schillinger; Timmy Hohnecker; Pan Qi; Katja Steiger; Michaela Aichler; Jürgen E. Gschwend; Roman Nawroth; Per Sonne Holm

doi:10.1038/s41467-022-32087-5

Nature Communications (Aug 2022)

Targeting the Retinoblastoma/E2F repressive complex by CDK4/6 inhibitors amplifies oncolytic potency of an oncolytic adenovirus

Jana Koch,
Sebastian J. Schober,
Sruthi V. Hindupur,
Caroline Schöning,
Florian G. Klein,
Klaus Mantwill,
Maximilian Ehrenfeld,
Ulrike Schillinger,
Timmy Hohnecker,
Pan Qi,
Katja Steiger,
Michaela Aichler,
Jürgen E. Gschwend,
Roman Nawroth,
Per Sonne Holm

Affiliations

Jana Koch: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Sebastian J. Schober: Department of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich
Sruthi V. Hindupur: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Caroline Schöning: Department of Pediatrics, Children’s Cancer Research Center, Kinderklinik München Schwabing, School of Medicine, Technical University of Munich
Florian G. Klein: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Klaus Mantwill: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Maximilian Ehrenfeld: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Ulrike Schillinger: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Timmy Hohnecker: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Pan Qi: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Katja Steiger: Department of Pathology, Klinikum rechts der Isar, Technical University of Munich
Michaela Aichler: Helmholtz Zentrum München, German Research Center for Environmental Health, Research Unit Analytical Pathology
Jürgen E. Gschwend: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Roman Nawroth: Department of Urology, Klinikum rechts der Isar, Technical University of Munich
Per Sonne Holm: Department of Urology, Klinikum rechts der Isar, Technical University of Munich

DOI: https://doi.org/10.1038/s41467-022-32087-5
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 18

Abstract

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Neither CDK4/6 inhibitors nor oncolytic adenoviruses show high efficiency as monotherapy in the treatment of cancer. Authors show here that when combined, CDK4/6 inhibitors deplete Retinoblastoma protein levels, which leads to more efficient virus replication and an increase in oncolytic virus-producing cancer cells and thus to efficient anti-tumor response in mouse xenograft sarcoma models.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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