Lysine-specific demethylase 1 as a therapeutic cancer target: observations from preclinical study

ABSTRACT

Introduction

Lysine-specific histone demethylase 1A (KDM1A/LSD1) has emerged as an important therapeutic target in various cancer types. LSD1 regulates a wide range of biological processes that influence cancer development, progression, metastasis, and therapy resistance. However, recent studies have revealed novel aspects of LSD1 biology, shedding light on its involvement in immunogenicity, antitumor immunity, and DNA damage response. These emerging findings have the potential to be leveraged in the design of effective LSD1-targeted therapies.

Areas covered

This paper discusses the latest developments in the field of LSD1 biology, focusing on its role in regulating immunogenicity, antitumor immunity, and DNA damage response mechanisms. The newfound understanding of these mechanisms has opened possibilities for the development of novel LSD1-targeted therapies for cancer treatment. Additionally, the paper provides an overview of LSD1 inhibitor-based combination therapies for the treatment of cancer.

Expert opinion

Exploiting LSD1 role in antitumor immunity and DNA damage response provides cues to not only understand the LSD1-resistant mechanisms but also rationally design new combination therapies that are more efficient and less toxic than monotherapy. The exploration of LSD1 biology and the development of LSD1-targeted therapies hold great promise for the future of cancer treatment.

KEYWORDS:

• LSD1/KDM1A
• antitumor immunity
• DNA damage response
• DNA repair
• immune therapies
• epigenetics
• combination therapies

Article highlights

• LSD1 is a recognized and established target for cancer therapy, and numerous LSD1 inhibitors are presently undergoing evaluation in clinical trials.

• LSD1 plays a critical role in governing a diverse array of biological processes. Recent research has illuminated its involvement in both antitumor immunity and the DNA damage response.

• Combining LSD1 inhibition with immune checkpoint inhibitors and agents that induce DNA damage holds significant promise as a strategy for cancer treatment.

• The potential therapeutic benefits of combining LSD1 inhibitors with other therapies warrant thorough investigation and further study.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by National Institutes of Health (NIH) grants 1R01NS106173-01A1 (GRS), T32CA148724 (JDJ), American Cancer Society Research Scholar Grant 132931-RSG-18-187-01-TBG (GRS), Department of Defense (DoD) Breast Cancer Research Program (BCRP) grant W81XWH-22-1-0013 (GRS), and METAvivor Translational Research Award (GRS).