Nadiia Lypova, PhD

Many patients with non-small cell lung cancer, driven by mutated EGFR gene, initially show positive responses to FDA-approved treatments such as osimertinib. However, these treatments are not always effective in eliminating all tumor cells. As a result, some surviving cells can eventually develop resistance to treatment, leading to a relapse of the disease. The adaptability of these cancer cells poses a significant challenge. There is a critical need to develop novel approaches to eradicate persister cells, which become tolerant to drugs. Our research has revealed that cells surviving during therapy adapt by altering their use of glucose and producing antioxidants, enabling them to resist treatment. We will take advantage of the metabolic shifts in surviving cells by disrupting glucose metabolism. We plan to create models to help us track the emergence of drug-resistant cells and assess the effectiveness of limiting metabolic reprogramming and existing treatments. We will identify metabolic vulnerabilities of persister cells and may find new treatment strategies to eliminate all tumor cells during the EGFR-targeting therapy.

Funded by the Courtney Cox Cole Lung Cancer Research Award

Update: We have developed both lab-based (in vitro) and tissue-based (ex vivo) lung cancer models that enable us to track drug-tolerant persister (DTP) cells in real-time during treatment with tyrosine kinase inhibitors (TKIs). Our organoid model closely mimics how patient tumors respond to TKIs, providing a solid foundation for future research. We are currently investigating how DTP cells survive by altering their metabolism and employing antioxidant defenses. We aim to gain a deeper understanding of how lung cancer develops resistance to treatment.