Lysine-Specific Demethylase 1 Promises to Be a Novel Target in Cancer Drug Resistance: Therapeutic Implications

Chemotherapy, targeted therapy, and immunotherapy are effective against most tumors, but drug resistance remains a barrier to successful treatment. Lysine-specific demethylase 1 (LSD1), a member of histone demethylation modifications, can regulate invasion, metastasis, apoptosis, and immune escape of tumor cells, which are associated with tumorigenesis and tumor progression. Recent studies suggest that LSD1 ablation regulates resensitivity of tumor cells to anticarcinogens containing immune checkpoint inhibitors (ICIs) via multiple upstream and downstream pathways. In this review, we describe the recent findings about LSD1 biology and its role in the development and progression of cancer drug resistance. Further, we summarize LSD1 inhibitors that have a reversal or resensitive effect on drug resistance and discuss the possibility of targeting LSD1 in combination with other agents to surmount resistance.

Automated summary

Chemotherapy, targeted therapy, and immunotherapy can effectively treat most tumors, but drug resistance limits their success. Lysine-specific demethylase 1 (LSD1) plays a role in regulating tumor cell invasion, metastasis, apoptosis, and immune evasion, which are associated with tumor development and progression. Recent studies have found that LSD1 inhibition can restore sensitivity of tumor cells to anticancer drugs containing immune checkpoint inhibitors (ICIs) through various pathways. This review discusses the role of LSD1 in cancer drug resistance and explores the potential of using LSD1 inhibitors in combination with other agents to overcome resistance.