Researchers at The Ohio State University Comprehensive Cancer Center (OSUCCC – James) have identified potential new therapies that may improve outcomes for patients with certain non-small cell lung cancers (NSCLC).
The study was published in Science Translational Medicine and led by Deliang Guo, PhD, and Yaogang Zhong, PhD, both with OSUCCC – James.
Key Discoveries
The research provides evidence for new therapies that target both lysosomes and the protein SREBP-1.
Lysosomes are cellular components involved in maintaining stability and nutrient availability. SREBP-1 increases glucose uptake and contributes to tumors' resistance to current therapies that inhibit lysosomes.
Unraveling Resistance Mechanisms
The study found that tumor cells can evade lysosomal suppression. Inhibiting glucose transport was shown to overcome tumor resistance to chloroquine (CQ) treatment by inducing mitochondrial damage, oxidative stress, and tumor cell death.
A Promising Therapeutic Strategy
The findings suggest a combination strategy targeting lysosomal function alongside glucose and lipid metabolism may effectively treat NSCLC.
This approach may also be applicable to other cancers with high metabolic demands for glucose and lipids. This strategy is noted as particularly suitable for patients with lung squamous cell carcinoma and subsets of lung adenocarcinoma who have limited treatment options.
Pathway to the Clinic
Existing drugs, chloroquine (CQ) and simvastatin, are clinically approved and repurposed. The fatty acid synthesis inhibitor TVB-2640 has entered phase II/III clinical trials, which could accelerate the clinical translation of this combination therapy strategy.