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Targeting the epigenetic addiction of Merkel cell carcinoma

Federico Mauri1, Cédric Blanpain1,2

  • 1Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium.

EMBO Molecular Medicine
|October 16, 2020
PubMed

Insights

Researchers found that inhibiting lysine-specific histone demethylase 1A (LSD1) selectively targets Merkel cell carcinoma (MCC). This approach promotes tumor cell differentiation, offering a promising new avenue for treating this rare and aggressive skin cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer.
  • Current therapeutic options for MCC are limited.
  • Immunotherapy shows efficacy in some MCC cases, but new treatments are needed.

Purpose of the Study:

  • To identify novel therapeutic vulnerabilities in Merkel cell carcinoma.
  • To investigate the potential of targeting lysine-specific histone demethylase 1A (LSD1) in MCC treatment.

Main Methods:

  • The study focused on identifying selective vulnerabilities in MCC.
  • The researchers investigated the effects of LSD1 inhibitors on MCC cells.
  • Tumor cell growth and differentiation were assessed in vivo.

Main Results:

  • Leiendecker et al. identified a selective vulnerability of MCC to LSD1 inhibitors.
  • LSD1 inhibitors were shown to promote differentiation of MCC tumor cells.
  • Inhibition of LSD1 impaired tumor cell growth in vivo.

Conclusions:

  • Targeting LSD1 represents a promising new therapeutic strategy for Merkel cell carcinoma.
  • LSD1 inhibition promotes a shift towards normal Merkel cell fate.
  • This approach opens new avenues for treating patients with MCC.

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