2023 World Conference on Lung Cancer (Posters)-P2.17. Characterizing Mechanisms of Treatment Resistance in SCLC

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Small cell lung cancer (SCLC) is an aggressive form of cancer with a poor prognosis. While SCLCs initially respond to chemotherapy, they often relapse in a treatment-resistant manner. The molecular mechanisms underlying this treatment resistance are not well understood. However, several studies have suggested that MYC family proteins, WNT and NOTCH signaling, EMT and differentiation pathways, and DNA repair pathways play a role in driving chemoresistance.<br /><br />To further investigate the mechanisms of treatment resistance in SCLC, researchers performed single-cell RNA sequencing (scRNAseq) on fresh tumor biopsies obtained from patients with relapsed SCLC. The data was analyzed along with data from previous studies and bulk whole-exome sequencing.<br /><br />The results showed that relapsed SCLCs exhibited markers of immune evasion, non-neuroendocrine subtypes, and epithelial-mesenchymal transition. Additionally, the relapsed and chemoresistant SCLC cells showed increased cell differentiation compared to chemotherapy-sensitive cells. These findings were validated using scRNAseq data from other studies that profiled SCLC specimens.<br /><br />This study contributes to our understanding of the molecular mechanisms driving treatment resistance in SCLC. By identifying markers of immune evasion and differentiation pathways, these findings provide potential targets for future therapeutic interventions to improve outcomes for patients with relapsed SCLC.

Asset Subtitle

Siddhartha Devarakonda

Meta Tag

Speaker Siddhartha Devarakonda

Topic SCLC & Neuroendocrine Tumors: Relapse & Salvage Therapy

Keywords

Small cell lung cancer

SCLC

aggressive cancer

chemotherapy resistance

MYC family proteins

WNT signaling

NOTCH signaling

EMT pathways

differentiation pathways

DNA repair pathways