Phosphoinositide 3'-kinase inhibition in chronic lymphocytic leukemia

Hematol Oncol Clin North Am. 2013 Apr;27(2):329-39. doi: 10.1016/j.hoc.2012.12.002.

Abstract

Phosphoinositide 3'-kinase (PI3K) is a key node in the B-cell receptor pathway, which plays a crucial role in the trafficking, survival, and proliferation of chronic lymphocytic leukemia (CLL) cells. This article reviews the biology of PI3K, focusing on its relationship to the CLL microenvironment, and discusses the biological rationale for PI3K inhibition in CLL. Preliminary safety and efficacy data from early phase clinical trials is also discussed. Potential biomarkers for clinical response to PI3K inhibitors such as ZAP-70, IGHV status, and CCL3 are examined. Where PI3K inhibition may fit in the evolving landscape of CLL therapy is also explored.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Prognosis
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • TOR Serine-Threonine Kinases