Tarantelli, Chiara Gaudio, Eugenio Hillmann, Petra Spriano, Filippo Sartori, Giulio Aresu, Luca Cascione, Luciano Rageot, Denise Kwee, Ivo Beaufils, Florent Zucca, Emanuele Stathis, Anastasios Wymann, Matthias P. Cmiljanovic, Vladimir Fabbro, Doriano Bertoni, Francesco 2019-06-04 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. application/pdf https://susi.usi.ch/global/documents/319122 https://n2t.net/ark:/12658/srd1319122 https://susi.usi.ch/documents/319122/files/Tarantelli_C_2019.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.3390/cancers11060775 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319122 info:eu-repo/semantics/openAccess CC BY Cancers. - 2019, vol. 11, no. 6, p. 775 Lymphoma mTORC1 mTORC2 Venetoclax Mantle cell lymphoma Diffuse large B cell lymphoma info:eu-repo/classification/udc/61 The novel TORC1/2 kinase inhibitor PQR620 has anti-tumor activity in lymphomas as a single agent and in combination with venetoclax http://purl.org/coar/resource_type/c_6501