{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:24:03Z","timestamp":1767626643545,"version":"3.40.5"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Gelu Foundation"},{"name":"Nelia et Amadeo Barletta Foundation"},{"name":"Acerta Pharma"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The B\u2010cell receptor and the phosphatidylinositol 3\u2010kinase (PI3K) signalling pathways, together with their downstream partners, represent important therapeutic targets for B\u2010cell lymphomas. Here, we evaluated the activity of acalabrutinib (ACP\u2010196) and ACP\u2010319 (AMG\u2010319), second generation inhibitors of Bruton tyrosine kinase (BTK) and PI3K\u03b4 inhibitor, respectively, in lymphoma pre\u2010clinical models. The two compounds showed activity in activated B\u2010cell\u2010like diffuse large B\u2010cell lymphoma (ABC DLBCL), mantle cell lymphoma and marginal zone lymphoma. Two <jats:italic>in vivo<\/jats:italic> experiments with ABC DLBCL and MCL xenografts confirmed the effect of the single agents. Benefit was achieved by exposing the lymphoma cell lines to both acalabrutinib and ACP\u2010319. Two cell lines presented a discordant response to first and second generation BTK inhibitors, probably due to the inhibition by ibrutinib of kinases other than BTK. In conclusion, our data sustain the on\u2010going current trials with acalabrutinib and ACP\u2010319 as single agents and provide the basis for the investigation of their combination as well.<\/jats:p>","DOI":"10.1111\/bjh.16118","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T14:56:43Z","timestamp":1564412203000},"page":"595-601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Single and combined BTK and PI3K\u03b4 inhibition with acalabrutinib and ACP\u2010319 in pre\u2010clinical models of aggressive lymphomas"],"prefix":"10.1111","volume":"187","author":[{"given":"Filippo","family":"Spriano","sequence":"first","affiliation":[{"name":"Institute of Oncology Research Universit\u00e0 della Svizzera italiana Bellinzona 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