Recent advancements of bortezomib in acute lymphocytic leukemia treatment

Acta Haematol. 2013;129(4):207-14. doi: 10.1159/000345260. Epub 2013 Jan 3.

Abstract

Although survival rates for acute lymphocytic leukemia (ALL), especially in children, have shown dramatic improvement over time, poor outcomes are still observed in patients who have refractory or relapsed disease after conventional chemotherapy. New therapeutic options are urgently needed. Bortezomib (Velcade, formerly PS-341) is the first proteasome inhibitor approved by the US FDA for the treatment of newly diagnosed multiple myeloma and relapsed/refractory multiple myeloma and mantle cell lymphoma. Although the mechanisms of bortezomib anticancer activity are still not completely understood, it is a new treatment option for patients with refractory or relapsed ALL, particularly when used in combination with conventional chemotherapy or targeted agents. This review summarizes recent advancements in the understanding of the bortezomib molecular mechanism of action in ALL. Understanding of the molecular approaches might help customize cancer chemotherapy for each individual patient, directing the field towards rational therapeutics.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Boronic Acids / adverse effects
  • Boronic Acids / pharmacology
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Drug Therapy, Combination
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / metabolism
  • Gastrointestinal Diseases / etiology
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Pyrazines / adverse effects
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Signal Transduction / drug effects
  • Thrombocytopenia / etiology
  • Valproic Acid / therapeutic use

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • Valproic Acid
  • Bortezomib
  • Fusion Proteins, bcr-abl
  • Proteasome Endopeptidase Complex