title: 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.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.|Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Maly
authors.affiliation: Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. james.blachly@osumc.edu.|The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. james.blachly@osumc.edu.
authors.forename: James S
authors.initials: JS
authors.lastname: Blachly
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072377:Syk Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000911:Antibodies, Monoclonal; D018797:Cell Cycle Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D051881:Receptor, Notch1; D000072377:Syk Kinase; C000625949:BTK protein, human
keywords: ACP-196; Chronic lymphocytic leukemia; Ibrutinib; Idelalisib; Novel therapy; Targeted therapy