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Epidermal growth factor receptor kinase substrate 8 (EPS8) is a versatile signaling adaptor protein that integrates growth factor receptor signaling with actin cytoskeleton dynamics [1, 5]. It functions as a key component of the EGFR pathway, facilitating the transduction of mitogenic signals and regulating cellular processes such as motility, endocytosis, and cell cycle progression [2, 15]. EPS8 is frequently overexpressed in a wide variety of malignancies, including solid tumors (e.g., pancreatic, breast, and colon cancers) and hematological malignancies, where it promotes aggressive phenotypes like invasion, metastasis, and drug resistance [1, 8, 11]. As a therapeutic target, EPS8 is being explored through the development of small molecules and inhibitory peptides designed to disrupt its interaction with partners like SOS1 and ABI1, thereby inhibiting oncogenic signaling cascades such as PI3K/AKT and Ras/Rac [2, 7, 8]. Additionally, EPS8 expression serves as a significant prognostic biomarker, with high levels often correlating with poor patient outcomes and reduced sensitivity to conventional chemotherapeutic agents [1, 15].
Inhibition of EPS8-mediated signaling pathways (e.g., PI3K/AKT, Ras/Rac) and disruption of protein-protein complexes like the SOS1/EPS8/ABI1 tri-complex to suppress tumor growth, invasion, and metastasis.
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