New drug discovery approaches targeting recurrent mutations in chronic lymphocytic leukemia

Expert Opin Drug Discov. 2017 Oct;12(10):1041-1052. doi: 10.1080/17460441.2017.1362387. Epub 2017 Aug 4.

Abstract

Next generation sequencing has provided a comprehensive understanding of the mutational landscape in chronic lymphocytic leukemia (CLL), and new drivers have been identified. Some of these drivers could be pharmacologically targeted to choose the most effective personalized therapy in each CLL patient. Areas covered: In this article, the authors uncover the potential role of new targeted therapies against the most recurrent mutations in CLL as well as the recently approved therapies. The authors also provide their expert opinion and give their perspectives for the future. Expert opinion: The development of more personalized therapies is of interest to clinicians as a system to enhance the duration of treatment response and to extend the survival and quality of life of CLL patients. The main challenge, however, will be to translate the preclinical results into the clinics. Therefore, the designing and execution of clinical trials focused on molecular drivers are the need of the hour.

Keywords: BCR signaling; BIRC3; MYD88; NOTCH1; SF3B1; chronic lymphocytic leukemia; recurrent mutations.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Drug Design
  • Drug Discovery / methods*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Molecular Targeted Therapy
  • Mutation
  • Precision Medicine
  • Quality of Life
  • Survival Rate

Substances

  • Antineoplastic Agents