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Open AccessArticle

The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax

1
Institute of Oncology Research, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
2
PIQUR Therapeutics AG, 4057 Basel, Switzerland
3
Dipartimento di Scienze Veterinarie, Università degli Studi di Torino, 10095 Grugliasco (TO), Italy
4
Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland
5
Department of Biomedicine, University of Basel, 4056 Basel, Switzerland
6
Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(6), 775; https://doi.org/10.3390/cancers11060775
Received: 10 March 2019 / Revised: 29 May 2019 / Accepted: 1 June 2019 / Published: 4 June 2019
(This article belongs to the Special Issue Protein Kinases and Cancers)
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Abstract

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. View Full-Text
Keywords: lymphoma; mTORC1; mTORC2; venetoclax; mantle cell lymphoma; diffuse large B cell lymphoma lymphoma; mTORC1; mTORC2; venetoclax; mantle cell lymphoma; diffuse large B cell lymphoma
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Tarantelli, C.; Gaudio, E.; Hillmann, P.; Spriano, F.; Sartori, G.; Aresu, L.; Cascione, L.; Rageot, D.; Kwee, I.; Beaufils, F.; Zucca, E.; Stathis, A.; Wymann, M.P.; Cmiljanovic, V.; Fabbro, D.; Bertoni, F. The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax. Cancers 2019, 11, 775.

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