Titles and Affiliations
Virginia G. Piper Center for Personalized Diagnostics
Professor of Chemistry and Biochemistry,
The Biodesign Institute
Research area
Identifying new therapeutic targets to treat highly aggressive breast cancers.
Impact
Triple-negative breast cancers (TNBC) are those that lack expression of estrogen receptor (ER), progesterone receptor (PR), and HER2. Because they lack an established target, TNBC is often difficult to treat. Dr. LaBaer is studying a tumor suppressor gene and the protein it encodes, called p53. Mutations in p53 are found in 80 percent of TNBC, making p53 a potential target for treating this aggressive subtype of breast cancer. However, researchers have struggled to find ways to target p53-mutated cancers. Dr. LaBaer’s work is aimed at identifying alternative targets for p53-mutant tumor cells. These may be other genes that work with p53 or other proteins that are activated by mutant p53. His findings could lead to the development of new combination approaches and personalized therapy for patients with TNBC.
Progress Thus Far
Thus far, Dr. LaBaer has discovered specific mutations that can initiate metastasis when p53 is mutated in TNBC. He and his team discovered that many of the aggressive and drug-resistant forms of TNBC share a common pathway called TAZ/TEAD signaling. Using advanced 3D tumor models and patient data, they confirmed that this pathway is strongly linked to cancer growth and resistance. Importantly, blocking TAZ/TEAD made certain p53-mutant cancers more sensitive to chemotherapy, suggesting a promising new combination treatment strategy. They also identified other gene mutations that partner with mutant p53 to drive cancer spread and also funnel into the same TAZ/TEAD pathway. Together, these findings point to TAZ/TEAD as a central vulnerability in aggressive TNBC that may be able to be exploited therapeutically.
What’s next
In the coming year, Dr. LaBaer and his team will build on their discoveries by digging deeper into how mutant p53 and its partner mutations drive aggressive, treatment-resistant breast cancers. The team will focus on the TAZ/TEAD pathway, which they now know acts as a common driver for cancer growth and drug resistance. They will investigate how different p53 mutations and their co-drivers affect this pathway, studying the key signals and protein interactions involved, and matching these findings with patient data to pinpoint new drug targets. The team will also explore how pathways that control circadian rhythm and cell growth signals work together with mutant p53 and TAZ/TEAD to fuel cancer spread. To test these ideas, they will use model systems that mimic the tumor environment. Finally, the team will explore new ways to block cancer-promoting communication between cells.
Biography
Joshua LaBaer is one of the nation’s foremost investigators in the rapidly expanding field of personalized medicine. Formerly director of the Harvard Institute of Proteomics (HIP), he was recruited to ASU’s Biodesign Institute as the first Piper Chair in Personalized Medicine. Dr. LaBaer’s efforts involve leveraging the Center’s formidable resources for the discovery and validation of biomarkers—unique molecular fingerprints of disease—which can provide early warning for those at risk of major illnesses, including cancer and diabetes. This work is carried out in conjunction with the Partnership for Personalized Medicine, a multi-institution effort that includes the Translational Genomics Research Institute in Phoenix and the Fred Hutchinson Cancer Research Institute in Seattle.
Dr. LaBaer is a board certified physician in Internal Medicine and Medical Oncology and was an Instructor and Clinical Fellow in Medicine at Harvard Medical School and now serves as Adjunct Professor of Medicine, Mayo Clinic. He has contributed to over 140 original research publications, is an associate editor of the Journal of Proteome Research, a member of the editorial boards of Analytical Biochemistry, Current Opinion in Biotechnology, Cancer Biomarkers, Molecular Biosystems, and Clinical Proteomics. Formerly a member of the NCI’s Board of Scientific Advisors, he serves as chair of the NCI’s Early Detection Research Network Executive Committee and Co-Chair of its Steering Committee. He is the president of the US Human Proteome Organization and serves on a number of government and industry scientific advisory boards. He earned his medical degree and doctorate (biochemistry and biophysics) at University of California, San Francisco.
