Adam Smith, PhD

Targeting oncogenic driver mutations, which are genetic mutations responsible for the initiation and maintenance of cancer, have revolutionized the treatment landscape for patients with lung cancer. The growth of next-generation sequencing-based biomarker testing, which looks for tumor markers that can provide information about cancer, has led to the discovery of recurrent cancer-causing variants. But for many of these variants the effect on protein structure and function is unknown (“variants of uncertain significance,” or VUS). This means there is not enough information to know if these variants are involved in cancer. These new data have exposed a critical unmet need to determine the effect of the VUSs and how they can be targeted therapeutically. We are focusing on lung cancer mutations in the EGFR gene. We will learn how EGFR VUS alter the interaction between EGFR and other membrane protein receptors. The insights generated will inspire new clinical strategies to treat lung cancer patients.

Update:

We are studying how a mutation in one protein may operate by changing how it interacts with another protein, thus driving irregular function in its binding partner. We are focusing on tumor-causing mutations in the EGFR gene at the protein level to determine how mutations affect interactions with other tumor markers like HER2.  This year we have discovered how EGFR variants alter the interaction network between EGFR and other membrane proteins. We have also discovered how HER2 variants alter EGFR-HER2 interactions. This research will allow us to unlock critical insights into the intricate interactions between EGFR-family proteins and their variants.