{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:30:34Z","timestamp":1761708634917},"reference-count":44,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Current research in lymphoma is focused on two areas of lymphoma biology\u2014the signal transduction pathways used to maintain the growth of malignant lymphocytes and the role of the tumor microenvironment in lymphoma growth and survival. This review focuses on three signaling pathways: the phosphatidylinositol 3-kinase\/mammalian target of rapamycin (PI3K\/mTOR) pathway, the B-cell receptor\/spleen tyrosine kinase (BCR\/Syk) pathway, and the protein kinase C-beta (PKC-\u03b2) pathway, known to be important to lymphoma cells. The mTOR inhibitors temsirolimus and everolimus have demonstrated antitumor activity in all types of lymphoma, the Syk inhibitor fostamatinib has activity in diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and the PKC-\u03b2 inhibitor enzastaurin is being used as consolidation therapy after remission in diffuse large B-cell lymphoma. This review discusses the biology behind the development of each new agent and the results of initial clinical trials. The goal is to provide the hematologist\/oncologist background information on these new agents and understand their current and potential role in the management of patients.<\/jats:p>","DOI":"10.1182\/asheducation-2010.1.265","type":"journal-article","created":{"date-parts":[[2011,1,16]],"date-time":"2011-01-16T19:08:48Z","timestamp":1295204928000},"page":"265-270","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":35,"title":["Signal Transduction Inhibitor Therapy for Lymphoma"],"prefix":"10.1182","volume":"2010","author":[{"given":"Thomas E.","family":"Witzig","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamta","family":"Gupta","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111709505576200_B1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s11864-006-0038-1","article-title":"Inhibition of the phosphatidylinositol 3-kinase\/mammalian target of rapamycin pathway in hematologic malignancies","volume":"7","author":"Witzig","year":"2006","journal-title":"Curr Treat Options Oncol"},{"key":"2019111709505576200_B2","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nrc1819","article-title":"Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis","volume":"6","author":"Cully","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"2019111709505576200_B3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.drup.2007.11.003","article-title":"Targeting the PI3K\/Akt\/mTOR pathway: effective combinations and clinical considerations","volume":"11","author":"LoPiccolo","year":"2008","journal-title":"Drug Resist Updat"},{"key":"2019111709505576200_B4","doi-asserted-by":"crossref","first-page":"7800","DOI":"10.1158\/0008-5472.CAN-04-4180","article-title":"Activation of mammalian target of rapamycin in transformed B lymphocytes is nutrient dependent but independent of Akt, mitogen-activated protein kinase\/extracellular signal-regulated kinase kinase, insulin growth factor-I, and serum","volume":"65","author":"Wlodarski","year":"2005","journal-title":"Cancer Res"},{"key":"2019111709505576200_B5","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/path.1725","article-title":"Constitutive activation of phosphatidyl-inositide 3 kinase contributes to the survival of Hodgkin's lymphoma cells through a mechanism involving Akt kinase and mTOR","volume":"205","author":"Dutton","year":"2005","journal-title":"J Pathol"},{"key":"2019111709505576200_B6","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1182\/blood-2009-05-220889","article-title":"Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2","volume":"114","author":"Gupta","year":"2009","journal-title":"Blood"},{"key":"2019111709505576200_B7","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bbapap.2009.12.001","article-title":"Dissecting the role of mTOR: Lessons from mTOR inhibitors","volume":"1804","author":"Dowling","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"2019111709505576200_B8","doi-asserted-by":"crossref","first-page":"727","DOI":"10.7164\/antibiotics.28.727","article-title":"Rapamycin (AY-22,989), a new antifungal antibiotic. 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