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Literature DB >> 26893063

Chronic Lymphocytic Leukemia: Exploiting Vulnerabilities with Targeted Agents.

Abstract

The field of oncology has been transformed over the course of the last 20 years in large part due to the enhanced understanding of cellular biology and cellular signaling. The indolent natural history of chronic lymphocytic leukemia (CLL) has permitted extensive study of cancer biology and can in some ways be thought of a model for understanding and translating concepts to other diseases. By systematically probing the biology of CLL cells and working out in stepwise fashion the transduction of signals from the surface immunoglobulin to nuclear transcription factors, investigators have paved the way for rational targeting of therapies at natural vulnerabilities that mimic oncogene addiction. These key targets include Bruton's tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), Src, Bcl2, and cyclin-dependent kinases (CDKs). In this review, we will consider these proteins and describe the current and future molecules designed to target them in CLL.

Entities: Chemical Disease Gene Mutation Species

Keywords: ACP-196; Chronic lymphocytic leukemia; Ibrutinib; Idelalisib; Novel therapy; Targeted therapy

Mesh：

Substances：

Year: 2016 PMID： 26893063 PMCID： PMC4969081 DOI： 10.1007/s11899-016-0299-0

Source DB: PubMed Journal: Curr Hematol Malig Rep ISSN： 1558-8211 Impact factor: 3.952

76 in total

1. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737.

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Journal: J Clin Invest Date: 2007-01 Impact factor: 14.808

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Authors: F K Stevenson; S S Sahota; C H Ottensmeier; D Zhu; F Forconi; T J Hamblin
Journal: Adv Cancer Res Date: 2001 Impact factor: 6.242

3. Proteasome inhibitor carfilzomib complements ibrutinib's action in chronic lymphocytic leukemia.

Authors: Betty Lamothe; Fabiola Cervantes-Gomez; Mariela Sivina; William G Wierda; Michael J Keating; Varsha Gandhi
Journal: Blood Date: 2015-01-08 Impact factor: 22.113

4. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia.

Authors: Xose S Puente; Magda Pinyol; Víctor Quesada; Laura Conde; Gonzalo R Ordóñez; Neus Villamor; Georgia Escaramis; Pedro Jares; Sílvia Beà; Marcos González-Díaz; Laia Bassaganyas; Tycho Baumann; Manel Juan; Mónica López-Guerra; Dolors Colomer; José M C Tubío; Cristina López; Alba Navarro; Cristian Tornador; Marta Aymerich; María Rozman; Jesús M Hernández; Diana A Puente; José M P Freije; Gloria Velasco; Ana Gutiérrez-Fernández; Dolors Costa; Anna Carrió; Sara Guijarro; Anna Enjuanes; Lluís Hernández; Jordi Yagüe; Pilar Nicolás; Carlos M Romeo-Casabona; Heinz Himmelbauer; Ester Castillo; Juliane C Dohm; Silvia de Sanjosé; Miguel A Piris; Enrique de Alava; Jesús San Miguel; Romina Royo; Josep L Gelpí; David Torrents; Modesto Orozco; David G Pisano; Alfonso Valencia; Roderic Guigó; Mónica Bayés; Simon Heath; Marta Gut; Peter Klatt; John Marshall; Keiran Raine; Lucy A Stebbings; P Andrew Futreal; Michael R Stratton; Peter J Campbell; Ivo Gut; Armando López-Guillermo; Xavier Estivill; Emili Montserrat; Carlos López-Otín; Elías Campo
Journal: Nature Date: 2011-06-05 Impact factor: 49.962

5. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets.

Authors: Andrew J Souers; Joel D Leverson; Erwin R Boghaert; Scott L Ackler; Nathaniel D Catron; Jun Chen; Brian D Dayton; Hong Ding; Sari H Enschede; Wayne J Fairbrother; David C S Huang; Sarah G Hymowitz; Sha Jin; Seong Lin Khaw; Peter J Kovar; Lloyd T Lam; Jackie Lee; Heather L Maecker; Kennan C Marsh; Kylie D Mason; Michael J Mitten; Paul M Nimmer; Anatol Oleksijew; Chang H Park; Cheol-Min Park; Darren C Phillips; Andrew W Roberts; Deepak Sampath; John F Seymour; Morey L Smith; Gerard M Sullivan; Stephen K Tahir; Chris Tse; Michael D Wendt; Yu Xiao; John C Xue; Haichao Zhang; Rod A Humerickhouse; Saul H Rosenberg; Steven W Elmore
Journal: Nat Med Date: 2013-01-06 Impact factor: 53.440

6. Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia.

Authors: Maria Ilaria Del Principe; Giovanni Del Poeta; Francesco Buccisano; Luca Maurillo; Adriano Venditti; Antonella Zucchetto; Rita Marini; Pasquale Niscola; Maria Antonietta Irno Consalvo; Carla Mazzone; Licia Ottaviani; Paola Panetta; Antonio Bruno; Riccardo Bomben; Giovanna Suppo; Massimo Degan; Valter Gattei; Paolo de Fabritiis; Maria Cantonetti; Francesco Lo Coco; Domenico Del Principe; Sergio Amadori
Journal: Blood Date: 2006-04-06 Impact factor: 22.113

7. Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor.

Authors: David Parry; Timothy Guzi; Frances Shanahan; Nicole Davis; Deepa Prabhavalkar; Derek Wiswell; Wolfgang Seghezzi; Kamil Paruch; Michael P Dwyer; Ronald Doll; Amin Nomeir; William Windsor; Thierry Fischmann; Yaolin Wang; Martin Oft; Taiying Chen; Paul Kirschmeier; Emma M Lees
Journal: Mol Cancer Ther Date: 2010-07-27 Impact factor: 6.261

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Authors: A Delmer; F Ajchenbaum-Cymbalista; R Tang; S Ramond; A M Faussat; J P Marie; R Zittoun
Journal: Blood Date: 1995-05-15 Impact factor: 22.113

9. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib.

Authors: Oliver Hantschel; Uwe Rix; Uwe Schmidt; Tilmann Bürckstümmer; Michael Kneidinger; Gregor Schütze; Jacques Colinge; Keiryn L Bennett; Wilfried Ellmeier; Peter Valent; Giulio Superti-Furga
Journal: Proc Natl Acad Sci U S A Date: 2007-08-07 Impact factor: 11.205