Tikvah Hayes, PhD

Lung cancer is the leading cause of cancer-related deaths worldwide. The most common type is called non-small cell lung cancer (NSCLC), which consists mostly of adenocarcinomas and squamous cell carcinomas. In about 15–20% of adenocarcinoma cases, the cancer is caused by changes in a gene called EGFR. This gene normally makes a protein that helps cells grow and divide in a healthy way. But when EGFR is changed, or mutated, it can send the wrong signals, causing cells to grow out of control and form cancers. There are already drugs that target some EGFR mutations. These medicines, called EGFR tyrosine kinase inhibitors, can be very effective for certain patients. However, they only work for specific mutations in one part of the EGFR protein. Other mutations, found in a different part of the protein called the extracellular domain (the section that sits outside the cell), don’t respond to any of the current treatments. These mutations are less common, but they still affect many people with lung cancer. Unfortunately, scientists know far less about them. Our project aims to change that. Using human lung cells and advanced 3D models called organoids, we are studying how these rare EGFR mutations cause cancer, how they interact with other cancer genes, and why today’s drugs don’t work. We are also using new genetic tools to search for weak spots in these cancer cells that could become targets for future medicines. By uncovering how these overlooked mutations drive cancer, we hope to open the door to better treatments for patients with lung cancer.