The novel TORC1/2 kinase inhibitor PQR620 has anti-tumor activity in lymphomas as a single agent and in combination with venetoclax
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Tarantelli, Chiara
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Gaudio, Eugenio
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Hillmann, Petra
PIQUR Therapeutics AG, 4057 Basel, Switzerland
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Spriano, Filippo
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Sartori, Giulio
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Aresu, Luca
Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, 10095 Grugliasco (TO), Italy
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Cascione, Luciano
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
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Rageot, Denise
Department of Biomedicine, University of Basel, 4056 Basel, Switzerland
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Kwee, Ivo
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
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Beaufils, Florent
PIQUR Therapeutics AG, 4057 Basel, Switzerland
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Zucca, Emanuele
Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland
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Stathis, Anastasios
Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland
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Wymann, Matthias P.
Department of Biomedicine, University of Basel, 4056 Basel, Switzerland
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Cmiljanovic, Vladimir
PIQUR Therapeutics AG, 4057 Basel, Switzerland
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Fabbro, Doriano
PIQUR Therapeutics AG, 4057 Basel, Switzerland
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Bertoni, Francesco
Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Published in:
- Cancers. - 2019, vol. 11, no. 6, p. 775
English
The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling cascade is an important therapeutic target for lymphomas. Rapamycin-derivates as allosteric mTOR complex 1 (TORC1) inhibitors have shown moderate preclinical and clinical anti-lymphoma activity. Here, we assessed the anti-tumor activity of PQR620, a novel brain penetrant dual TORC1/2 inhibitor, in 56 lymphoma cell lines. We observed anti-tumor activity across 56 lymphoma models with a median IC50 value of 250 nM after 72 h of exposure. PQR620 was largely cytostatic, but the combination with the BCL2 inhibitor venetoclax led to cytotoxicity. Both the single agent and the combination data were validated in xenograft models. The data support further evaluation of PQR620 as a single agent or in combination with venetoclax.
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Medicine
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https://n2t.net/ark:/12658/srd1319122
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