2024 World Conference on Lung Cancer (WCLC) - Posters-P3.13D.03 Inhibition of LSD1 Prevented Tumor Progression and Recurrence to Radioimmunotherapy in Small Cell Lung Cancer

P3.13D.03 Inhibition of LSD1 Prevented Tumor Progression and Recurrence to Radioimmunotherapy in Small Cell Lung Cancer

Pdf Summary

The study investigates the role of LSD1 inhibition in preventing tumor progression and recurrence in small cell lung cancer (SCLC) following radioimmunotherapy. SCLC is known for its aggressiveness and poor prognosis, despite the promising synergistic effects of combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs). However, tumor recurrence remains a challenge. The research aimed to explore the mechanisms behind SCLC relapse in the context of this combination therapy and to identify new therapeutic targets.<br /><br />In the study, a mouse model of SCLC was used, where tumors were subjected to RT and anti-PD-1 antibody treatment. It was observed that while initial treatment showed effectiveness, T cells in the tumors returned to baseline levels by day 18, which corresponded with tumor recurrence and progression. Organoids derived from mouse lung tissues were used to further understand gene disruptions associated with human SCLC.<br /><br />The key finding was an upregulation of LSD1 in recurrent SCLC, suggesting that LSD1-positive tumor cells may be resistant to RT and ICI treatment, contributing to recurrence and progression. By targeting LSD1, the study showed that tumor growth could be delayed, and survival improved. This effect was achieved through the enhancement of antigen presentation and the downregulation of the epithelial-mesenchymal transition (EMT) pathway.<br /><br />The study proposes that a triple therapy approach, combining RT, ICI, and an LSD1 inhibitor, could be a more effective strategy for managing SCLC, potentially reducing the risk of tumor recurrence and improving patient outcomes.

Asset Subtitle

Feifei Na

Meta Tag

Speaker Feifei Na

Topic SCLC & Neuroendocrine Tumors

Keywords

LSD1 inhibition

tumor progression

small cell lung cancer

radioimmunotherapy

immune checkpoint inhibitors

tumor recurrence

antigen presentation

epithelial-mesenchymal transition

triple therapy

therapeutic targets