title: NOTCH and PI3K-AKT pathways intertwined.
abstract: Constitutive signaling by the NOTCH1 receptor contributes to more than half of all cases of T cell acute lymphoblastic leukemia (T-ALL). However, blocking the proteolytic activation of NOTCH1 with gamma-secretase inhibitors (GSIs) fails to alter the growth of some T-ALL cell lines carrying the mutated receptor. A recent report by Palomero et al. in Nature Medicine identifies loss of PTEN as a critical event leading to resistance to NOTCH inhibition, which causes the transfer of "oncogene addiction" from the NOTCH1 to the PI3K/AKT pathway. This novel observation suggests the need to simultaneously inhibit both pathways as a means to improve therapeutic efficacy in human T-ALL.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gutierrez
authors.forename: A Thomas
authors.initials: AT
authors.lastname: Look
mesh_terms: D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015458:Leukemia, T-Cell / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009857:Oncogenes / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt