title: GS-1101: a delta-specific PI3K inhibitor in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) remains an incurable B-cell malignancy with many unanswered questions. While the cell of origin and etiology are still unknown, significant scientific progress has revealed numerous molecular targets for novel therapeutic interventions. Phosphatidylinositol 3-kinases (PI3K) regulate key cellular functions, including growth, survival and migration, by integrating and transmitting signals from diverse surface molecules including the B-cell receptor (BCR). In lymphocytes, the PI3Kδ isoform plays a critical role in B-cell homeostasis and function. In CLL, the PI3K pathway is constitutively active and dependent on PI3Kδ. GS-1101 is a highly selective PI3Kδ inhibitor that in CLL patients causes a rapid and sustained reduction in lymphadenopathy, accompanied by transient lymphocytosis. This article will review new insights into the pathophysiology of CLL, the preclinical rationale of a PI3Kδ inhibitor in CLL, and the clinical evidence supporting this first-in-class therapeutic target for CLL patients.
authors.affiliation: Hematologic Malignancies Research, Sarah Cannon Research Institute, 3322 West End Avenue, Suite 900, Nashville, TN 37203, USA. imaciasperez@gmail.com
authors.forename: Ines M
authors.initials: IM
authors.lastname: Macias-Perez
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000503:physiopathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use*; D052999:Quinazolinones / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; C552946:idelalisib