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Critical Reviews™ in Oncogenesis

Published 4 issues per year

ISSN Print: 0893-9675

ISSN Online: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

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Targeting NOTCH1 in Hematopoietic Malignancy

Volume 16, Issue 1-2, 2011, pp. 103-115
DOI: 10.1615/CritRevOncog.v16.i1-2.100
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ABSTRACT

NOTCH1 is a well-validated target in hematopoietic malignancy, with NOTCH1 activating mutations identified in more than 50% of T-cell acute lymphoblastic leukemias. Moreover, a recent report has identified NOTCH1 activating mutations in 12% of chronic lymphocytic leukemias. While the frequency of NOTCH1 mutations and the well-documented role of this protein in the pathogenesis and maintenance of T-ALL support targeting NOTCH1 as a therapeutic strategy, the critical role of this protein in normal cell-fate specification and differentiation lead to complexities in its successful targeting. In this review, we will discuss potential approaches to targeting NOTCH1 in hematopoietic malignancies, including inhibition of the enzymes involved in its activation, antibodies directed against either the receptor or its ligands, and direct interference with the NOTCH1 transcriptional complex. Moreover, we will discuss the challenges to each of these approaches as well as potential solutions to overcoming these difficulties.

CITED BY
  1. Roti Giovanni, Carlton Anne, Ross Kenneth N., Markstein Michele, Pajcini Kostandin, Su Angela H., Perrimon Norbert, Pear Warren S., Kung Andrew L., Blacklow Stephen C., Aster Jon C., Stegmaier Kimberly, Complementary Genomic Screens Identify SERCA as a Therapeutic Target in NOTCH1 Mutated Cancer, Cancer Cell, 23, 3, 2013. Crossref

  2. Bertrand Fred E., McCubrey James A., Angus C. William, Nutter Jennifer M., Sigounas George, NOTCH and PTEN in prostate cancer, Advances in Biological Regulation, 56, 2014. Crossref

  3. Baldoni Stefano, Del Papa Beatrice, Dorillo Erica, Aureli Patrizia, De Falco Filomena, Rompietti Chiara, Sorcini Daniele, Varasano Emanuela, Cecchini Debora, Zei Tiziana, Di Tommaso Ambra, Rosati Emanuela, Alexe Gabriela, Roti Giovanni, Stegmaier Kimberly, Di Ianni Mauro, Falzetti Franca, Sportoletti Paolo, Bepridil exhibits anti-leukemic activity associated with NOTCH1 pathway inhibition in chronic lymphocytic leukemia, International Journal of Cancer, 143, 4, 2018. Crossref

  4. You M. James, Medeiros L. Jeffrey, Hsi Eric D., T-Lymphoblastic Leukemia/Lymphoma, American Journal of Clinical Pathology, 144, 3, 2015. Crossref

  5. Follini Elena, Marchesini Matteo, Roti Giovanni, Strategies to Overcome Resistance Mechanisms in T-Cell Acute Lymphoblastic Leukemia, International Journal of Molecular Sciences, 20, 12, 2019. Crossref

  6. Pagliaro Luca, Marchesini Matteo, Roti Giovanni, Targeting oncogenic Notch signaling with SERCA inhibitors, Journal of Hematology & Oncology, 14, 1, 2021. Crossref

  7. La Starza Roberta, Cambò Benedetta, Pierini Antonio, Bornhauser Beat, Montanaro Anna, Bourquin Jean-Pierre, Mecucci Cristina, Roti Giovanni, Venetoclax and Bortezomib in Relapsed/Refractory Early T-Cell Precursor Acute Lymphoblastic Leukemia, JCO Precision Oncology, 3, 2019. Crossref

  8. Marchesini Matteo, Gherli Andrea, Montanaro Anna, Patrizi Laura, Sorrentino Claudia, Pagliaro Luca, Rompietti Chiara, Kitara Samuel, Heit Sabine, Olesen Claus E., Møller Jesper V., Savi Monia, Bocchi Leonardo, Vilella Rocchina, Rizzi Federica, Baglione Marilena, Rastelli Giorgia, Loiacono Caterina, La Starza Roberta, Mecucci Cristina, Stegmaier Kimberly, Aversa Franco, Stilli Donatella, Lund Winther Anne-Marie, Sportoletti Paolo, Bublitz Maike, Dalby-Brown William, Roti Giovanni, Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia, Cell Chemical Biology, 27, 6, 2020. Crossref

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