BRAF inhibitor therapy in HCL

Best Pract Res Clin Haematol. 2015 Dec;28(4):246-52. doi: 10.1016/j.beha.2015.10.001. Epub 2015 Oct 20.

Abstract

Targeted treatment approaches are transforming the therapeutic landscape of cancer care. The discovery of the BRAF V600E mutation in most cases of classical hairy cell leukemia opens up unique opportunities for tumor specific treatment of HCL targeting the MEK/ERK signaling pathway. The discovery and biological implications of BRAF V600E in HCL are summarized to form a basis for our current understanding of the potential for clinical exploitation. There is overwhelming clinical evidence for activity of inhibitors of BRAF in the disease. The review will review current trial activity as well as discuss novel trial concepts exploiting targeted treatment focusing on BRAF inhibition in HCL.

Keywords: BRAF V600E; BRAF inhibitor; Dabrafenib; Hairy cell leukemia; MEK; Vemurafenib.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Imidazoles / therapeutic use*
  • Indoles / therapeutic use*
  • Leukemia, Hairy Cell / drug therapy*
  • Leukemia, Hairy Cell / genetics
  • Leukemia, Hairy Cell / mortality
  • Leukemia, Hairy Cell / pathology
  • MAP Kinase Signaling System / drug effects
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasm, Residual
  • Oximes / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Remission Induction
  • Sulfonamides / therapeutic use*
  • Survival Analysis
  • Vemurafenib

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Indoles
  • Oximes
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • dabrafenib