Titles and Affiliations
Pittsburgh Foundation Chair and Director, Institute for Precision Medicine
Professor, Pharmacology & Chemical Biology, and Human Genetics
UPMC Hillman Cancer Center
Research area
Improving treatment for invasive lobular breast cancer by inhibiting tumor growth.
Impact
Invasive lobular cancer (ILC) accounts for 10-15% of all breast cancers. While an estrogen receptor (ER)-positive breast cancer, the unique biology of ILC distinguishes it from other ER-positive diseases. As a discrete breast cancer subtype, ILC is the sixth most common cancer in women. The major feature of ILC is mutation and subsequent loss of E-cadherin, a cell adhesion protein molecule important to normal breast tissue architecture. Dr. Lee and his team study the unique features of ILC.
Progress Thus Far
Over the past year, Dr. Lee and his team have made major strides in understanding how certain gene changes drive ILC. Using large patient datasets, they found that mutations in the HER2 gene are more common in metastatic ER-positive, HER2-negative ILC and are linked to worse outcomes. In laboratory models, these HER2 mutations made cancer cells more active but also more vulnerable to HER2-targeted treatments like neratinib (Nerlynx®) and trastuzumab deruxtecan (T-DXd, Enhertu®) suggesting new treatment opportunities.
What’s next
In the coming year, they will take a deeper dive into the DNA sequencing data to uncover more details about ILC tumor biology. They aim to refine experiments that track how proteins called YAP and TEAD4 may switch on HER2 mutations in ILC. Early findings also suggest that HER3, another related protein that promotes cell proliferation, may play a role in activating HER2-mutant cells, so they will investigate how these two proteins interact in cancer cells. They will further study whether blocking HER3, on its own or together with HER2-targeting drugs such as T-DXd, could be an effective strategy for treating patients with HER2-mutant ILC.
Biography
Adrian Lee, PhD is the Pittsburgh Foundation Chair and Director of the Institute for Precision Medicine at the University of Pittsburgh and UPMC. He is Professor of Pharmacology and Chemical Biology, and Professor of Human Genetics, at UPM Hillman Cancer Center and Magee Women’s Research Institute. Dr. Lee received his BSc and PhD in England and came to San Antonio for his postdoctoral studies. He was subsequently recruited to Baylor College of Medicine and now the University of Pittsburgh.
The goal of Dr. Lee’s laboratory is to translate basic cell and molecular research findings into the understanding and treatment of breast cancer. Dr. Lee serves on numerous other national peer-review committees and is on the Scientific Advisory Board for Susan G. Komen for the Cure.
