For aggressive cancers like non-small-cell lung cancer (NSCLC) with KRAS/LKB1 mutations, tumors quickly adapt to single-agent treatments, developing resistance and creating a major roadblock. To overcome this, a new approach is in need: combination therapy.
By attacking cancer from multiple, cooperative angles, we can expose hidden vulnerabilities. TD2 Oncology set out to do just that, by combining a MEK-inhibitor and a Class I/IIb HADC inhibitor, and it worked.
Panome Bio’s Next Generation Metabolomics® platform revealed how.
A549 (epithelial human lung carcinoma) xenograft mouse model was used to evaluate the therapeutic effects of the GB-3103 (a Class I/IIb HDAC inhibitor) and Trametinib, both alone and in combination.
Untargeted metabolomics profiling was performed using Panome Bio’s Next-Generation Metabolomics platform providing high-resolution insights into treatment induced metabolic reprogramming and supporting the development of targeted combination therapies.
Detecting Tumor Growth
The results are clear, while individual drugs showed some promise, the combination therapy delivered a strong results: a significant reduction in tumor growth. But how?
Detecting Synergy with Metabolomics
Panome Bio’s global, untargeted metabolomics analysis showed something remarkable: the drug combination did more than just act in parallel. It induced a potent metabolic synergy, overwhelming the tumor in a way a single drug can’t reach.
By mapping over 3,900 metabolites, Panome Bio identified key metabolic pathways that were significantly altered.
A New Kind of Metabolic Stress
The data revealed a clear pattern: the dual treatment not only blocks growth-promoting pathways but also puts a massive burden on the tumor cells.
- Starved from Within: It starved the tumor cells by depleting key lipids needed for growth and energy
- Overwhelmed and Vulnerable: It created massive oxidative stress, elevating key metabolites that made the tumor cells far more vulnerable to treatment
The future of precision oncology starts with true biological understanding. Panome Bio’s validated workflow expands what’s possible in cancer research. Advance your combination therapy studies Next-Generation Metabolomics. We help you turn complex treatment data into clear information, giving researchers a reliable way to understand metabolic reprogramming, optimize combination therapy and drive precision oncology forward.
Application Note: Metabolomics for Mechanism of Action: Understanding Drivers of Synergistic Inhibitor Treatment in Cancer
Explore our latest Blog: A Metabolic Blueprint for Synergistic Cancer Therapy: Observations from Panome Bio & TD2 Oncology
Unlock Deeper Insights with Panome Bio
Panome Bio’s Next-Generation Metabolomics enables high-quality detection, helping you save time and resources. Go beyond simple comparisons to explore large cohorts and longitudinal studies. Our advanced platform delivers a global, qualitative view of metabolism, with powerful computational tools to make sense of complex data.
Contact us to start your project.