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The Histone Demethylase LSD1/ΚDM1A Mediates Chemoresistance in Breast Cancer via Regulation of a Stem Cell Program

John Verigos1,2, Panagiotis Karakaidos3,4, Dimitris Kordias5,6

  • 1Institute of Molecular Biology and Biotechnology-Foundation for Research and Technology, 45110 Ioannina, Greece. ioan_ver@yahoo.gr.

Cancers
|October 20, 2019
PubMed

Insights

Lysine-specific demethylase 1 (LSD1) is crucial for breast cancer stemness and chemoresistance. Inhibiting LSD1 alongside chemotherapy effectively eliminates cancer cells, offering a promising new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Breast cancer remains a leading cause of cancer death in women, with heterogeneity and drug resistance posing significant therapeutic challenges.
  • Cancer stem cells (CSCs) are implicated in tumor recurrence and resistance to conventional treatments.
  • Identifying novel therapeutic targets is critical for improving breast cancer outcomes.

Purpose of the Study:

  • To investigate the role of lysine-specific demethylase 1 (LSD1) in breast cancer chemoresistance and stemness.
  • To evaluate LSD1 as a potential therapeutic target for overcoming drug resistance in breast cancer.

Main Methods:

  • In vitro and in vivo assays were conducted to assess LSD1's function in breast cancer cells.
  • The efficacy of combining LSD1 inhibitors with conventional anti-cancer drugs was evaluated in a 3D spheroid system.

Main Results:

  • LSD1 was found to be critical in maintaining the pool of tumor-initiating cells responsible for drug resistance.
  • Combined administration of LSD1 inhibitors and anti-cancer drugs demonstrated superior efficacy in eliminating all tumor cells compared to monotherapy.
  • LSD1 inhibition significantly impacts breast cancer stemness.

Conclusions:

  • LSD1 is a key regulator of breast cancer stemness and chemoresistance.
  • Targeting LSD1 presents a promising strategy for developing novel combination therapies to combat breast cancer recurrence and drug resistance.
Keywords:
KDM1Abreast cancer stem cellscombination therapylysine-specific demethylase 1self-renewaltherapy resistancetumor heterogeneitytumor initiation

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