WCLC 2025 - Posters & ePosters-EP.03.06 Blocking JNK Signaling as a Strategy to Fight EGFR-Driven Lung Cancer

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This research, presented by Leizhi Shi, investigates therapeutic strategies against lung cancer driven by constitutively active Epidermal Growth Factor Receptor (EGFR) signaling, focusing on the downstream pathways involved in tumor development and progression. Using airway stem cells as a model, the study demonstrates that persistent EGFR activation induces tumor-like growth.<br /><br />Key findings highlight that EGFR activation predominantly stimulates the PI3K/AKT pathway, which promotes cell survival by inhibiting apoptosis but does not significantly reduce cell proliferation when blocked. Inhibiting PI3K in EGFR-driven tumors results mainly in increased apoptosis without affecting mitosis, indicating that targeting PI3K alone is insufficient to halt tumor growth.<br /><br />The study also examines the role of the JAK/STAT signaling pathway. Specifically, RNA interference-mediated blockade of STAT92E, a critical transcription factor in the pathway, fails to rescue EGFR-induced tumor-like proliferation or apoptosis inhibition. Although blocking STAT signaling does not reverse tumor growth or survival effects, it does reduce EGFR-driven cell migration, suggesting its involvement in tumor cell motility rather than proliferation or survival.<br /><br />Collectively, these results imply that while the PI3K/AKT axis mainly supports tumor cell survival downstream of EGFR, and JAK/STAT signaling influences migration, neither pathway alone fully mediates tumor growth caused by EGFR activation. These insights suggest that targeting c-Jun N-terminal kinase (JNK) signaling, potentially identified in other parts of the study (implied by the title), might present a more effective strategy for combating EGFR-driven lung cancer by interfering with critical proliferative and survival pathways in tumor stem cells.<br /><br />This work emphasizes the complexity of EGFR-driven lung tumor biology and the need for multi-targeted therapeutic approaches beyond PI3K and JAK/STAT inhibition in order to effectively control tumor development and progression.

Asset Subtitle

Leizhi Shi

Meta Tag

Speaker Leizhi Shi

Topic Tumor Biology – Translational Biology

Keywords

EGFR-driven lung cancer

Epidermal Growth Factor Receptor

PI3K/AKT pathway

JAK/STAT signaling

tumor cell survival

apoptosis inhibition

airway stem cells

cell migration

tumor proliferation

multi-targeted therapy