The impact of fusion genes on cancer stem cells and drug resistance

Mol Cell Biochem. 2021 Oct;476(10):3771-3783. doi: 10.1007/s11010-021-04203-4. Epub 2021 Jun 7.

Abstract

With ever increasing evidences on the role of fusion genes as the oncogenic protagonists in myriad cancers, it's time to explore if fusion genes can be the next generational drug targets in meeting the current demands of higher drug efficacy. Eliminating cancer stem cells (CSC) has become the current focus; however, we have reached a standstill in drug development owing to the lack of effective strategies to eradicate CSC. We believe that fusion genes could be the novel targets to overcome this limitation. The intriguing feature of fusion genes is that it dominantly impacts every aspect of CSC including self-renewal, differentiation, lineage commitment, tumorigenicity and stemness. Given the clinical success of fusion gene-based drugs in hematological cancers, our attempt to target fusion genes in eradicating CSC can be rewarding. As fusion genes are expressed explicitly in cancer cells, eradicating CSC by targeting fusion genes provides yet an another advantage of negligible patient side effects since normal cells remain unaffected by the drug. We hereby delineate the latest evidences on how fusion genes regulate CSC and drug resistance.

Keywords: Cancer stem cells; Drug resistance; Fusion genes; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Resistance, Neoplasm / genetics*
  • Genes, Neoplasm*
  • Humans
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Oncogene Proteins, Fusion* / genetics
  • Oncogene Proteins, Fusion* / metabolism

Substances

  • Oncogene Proteins, Fusion