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Research Update: Using T cells to Tackle Drug Resistance in EGFR+ Lung Cancer

*March 2024*

Approximately 10%-15% of patients with non-small cell lung cancer have tumors with mutations in the EGFR (epidermal growth factor receptor) gene. EGFR mutations are known to drive cancer growth. Many patients living with EGFR-positive lung cancer benefit from targeted therapies called tyrosine kinase inhibitors (TKIs). TKIs, such as osimertinib, can help patients by specifically blocking the effect of these mutations and reducing tumor growth. However, TKI-treated tumors eventually develop drug resistance, evade treatment, and resume growth.

To help address this increasing problem of drug resistance, EGFR Resisters, a community led by patients (and caregivers) advocating for improved treatment options for people with EGFR-positive lung cancer, partnered with LUNGevity for the second time to support research in this area. Alexandre Reuben, PhD, assistant professor in the Department of Thoracic/Head & Neck Medical Oncology at MD Anderson Cancer Center, received an EGFR Resisters/LUNGevity Research Award for EGFR-Positive Lung Cancer in 2023. LUNGevity spoke with Dr. Reuben to learn more about his research to improve outcomes for patients living with EGFR-positive lung cancer.

LUNGevity Foundation: Why is it important to support lung cancer research?

Dr. Alexandre Reuben: Lung cancer is the leading cause of cancer death in the United States. However, lung cancer research is severely underfunded when compared to other cancers like breast and colon cancers. There is also a stigma associated with lung cancer. Some people believe that because of a history of active tobacco exposure, a person brought the disease upon themselves. While we know that tobacco exposure increases the risk of some types of lung cancer, we are learning that there are other factors too. This is just one example of why it’s extremely important to support lung cancer research. We need to continue learning about this disease and leveraging this knowledge to help patients.

LF: Tell us about the work you do in your laboratory. 

AR: My background is in immunology. I specifically study T cells, an important part of the body’s natural defense mechanisms. We know that genetic mutations occur naturally as cells copy their DNA and divide. Sometimes these mutations happen in key genes and contribute to tumor development. The body’s immune system has developed ways to recognize this cellular damage and protect us from genetic mutations daily by removing these cells. However, in the case of cancer, the tumor cells find ways to avoid the immune system and continue growing.

I’ve been interested in this interaction between the immune system and tumor cells for a while. Over the past five years, my lab focused on T cell engineering. T cells are a part of our immune system and help fight infections and protect us from disease. We take T cells and modify specific receptors found on their cell surfaces. The hope is that these modified T cell receptors will allow the immune system to better identify and kill tumor cells.

LF: Describe your research project that is being co-funded by EGFR Resisters and LUNGevity?

AR: The thing is, I’m a researcher, not a medical doctor. I don’t see patients and I’m not an expert in EGFR. I’m an immunologist. This grant has given me the opportunity to partner with my Co-PI (co-principal investigator) Dr. John Heymach, who is a world-renowned expert on EGFR. He is interested in finding new ways to address a major challenge facing patients with EGFR-positive lung cancer—drug resistance.

Working together, we saw that the receptors developed in my lab might be useful to the EGFR community. We aim to use the T cells with modified receptors to target drug-tolerant persister cells, or DTPCs. DTPCs are tumor cells that remain alive after treatment and eventually cause the tumor to grow again.

LF: If this research is successful, what does it mean for the lung cancer community.

AR: Our goal is to use T cell engineering to stop DTPCs from growing and ultimately prevent the development of drug resistance in patients who are living with EGFR-positive lung cancer. This would improve not only the duration of their lives, but also the quality. Read more.

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