Mechanisms of Resistance and Implications for Treatment Strategies in Chronic Myeloid Leukaemia

Govinda Poudel, Molly G. Tolland, Timothy P. Hughes, Ilaria S. Pagani

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

Tyrosine kinase inhibitors (TKIs) have revolutionised the management of chronic myeloid leukaemia (CML), with the disease now having a five-year survival rate over 80%. The primary focus in the treatment of CML has been on improving the specificity and potency of TKIs to inhibit the activation of the BCR::ABL1 kinase and/or overcoming resistance driven by mutations in the BCR::ABL1 oncogene. However, this approach may be limited in a significant proportion of patients who develop TKI resistance despite the effective inhibition of BCR::ABL1. These patients may require novel therapeutic strategies that target both BCR::ABL1-dependent and BCR::ABL1-independent mechanisms of resistance. The combination treatment strategies that target alternative survival signalling, which may contribute towards BCR::ABL1-independent resistance, could be a successful strategy for eradicating residual leukaemic cells and consequently increasing the response rate in CML patients.

Original languageEnglish
Article number3300
JournalCancers
Volume14
Issue number14
DOIs
Publication statusPublished or Issued - 1 Jul 2022

Keywords

  • BCR::ABL1-independent mechanism of TKI resistance
  • chronic myeloid leukaemia
  • combination treatments
  • therapy resistance
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this