Targeted therapy in T-cell malignancies: dysregulation of the cellular signaling pathways.
T-cell malignancies, mainly known as T-cell acute lymphoblastic leukemia (T-ALL) and T-cell non-Hodgkin's lymphoma (T-NHL), are aggressive tumors. Although the clinical outcome of the patients has improved dramatically with combination chemotherapy, significant challenges remain, including understanding of the factors that contribute to the malignant behavior of these tumor cells and developing subsequently optimal targeted therapy. Aberrant cell signal transduction is generally involved in tumor progression and drug resistance. This review describes the pathogenetic role of multiple cellular signaling pathways in T-cell malignancies and the potential therapeutic strategies based on the modulation of these key signaling networks.
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai 200025, China. weili_zhao_sih@yahoo.com
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D000818:Animals; D006801:Humans; D053614:Janus Kinase 2 / Q000502:physiology; D016399:Lymphoma, T-Cell / Q000188:drug therapy*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000502:physiology; D050778:NFATC Transcription Factors / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000503:physiopathology; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D051881:Receptor, Notch1 / Q000502:physiology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D053614:Janus Kinase 2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D051881:Receptor, Notch1; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D050799:STAT5 Transcription Factor; D058570:TOR Serine-Threonine Kinases; C497761:NOTCH1 protein, human; C499374:NOTCH3 protein, human; C546842:MTOR protein, human