The “LKB1 connection”: role of LKB1 loss in promoting NSCLC aggressiveness through tumor microenvironment corruption

Lung cancers with LKB1 mutations (about 15% of non-small cell lung cancers) are highly aggressive, prone to early metastasis, and often resistant to current therapies. Our project investigates how these tumors manipulate the tumor microenvironment (TME) to create a “pro-disseminating” niche that supports cancer growth and spread.

We will:

• Characterize the secreted molecules (proteins, lipids, metabolites) of LKB1-mutated tumors.
• Study how these secreted factors affect surrounding cells, such as fibroblasts, endothelial cells, immune cells, and epithelial cells.
• Validate key findings in patient samples and preclinical models, exploring new combination strategies with chemotherapy, metformin, and immunotherapy.

This research aims to identify the molecular “language” through which LKB1-mutated tumors corrupt the TME, paving the way for new biomarkers and therapeutic approaches for patients with these aggressive lung cancers.