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The Role of Hedgehog Signaling in Non-small Cell Lung Cancer: Targeting Tumor Invasion, Therapy Resistance and Novel Therapeutic Strategies

Year: 2025

Type: article

Abstract: Although essential for normal development and tissue homeostasis, aberrant activation of the Hedgehog (Hh) signaling pathway is implicated in non-small cell lung cancer (NSCLC) progression and treatment resistance. This review details the contribution of Hh signaling to NSCLC, focusing on its promotion of tumor invasion and therapeutic resistance, and establishes a rationale for disrupting this pathway to improve treatment efficacy. Malignant phenotypes in NSCLC are driven by dysregulated Hh pathway activity, often via autocrine or paracrine loops. We specifically assess how Hh pathway activation enables tumor invasion, metastasis, and the development of drug resistance. The review elucidates key resistance mechanisms against diverse therapies-encompassing chemotherapy, targeted therapy and immunotherapy-with a focus on epithelial-mesenchymal transition (EMT), cancer stem cell maintenance, and multidrug resistance (MDR). Therefore, combining Hh pathway inhibitors with standard therapies represents a promising approach for managing treatment-resistant NSCLC.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.123287

Authors: Yu Kang, Hongmei Zheng, Qiuyuan Wen, Songqing Fan

Institutions: Central South University, Second Xiangya Hospital of Central South University

Language: English

Topic: Hedgehog Signaling Pathway Studies

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,337