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Valerie Weaver, PhD
Professor & Director, Center for Bioengineering and Tissue Regeneration
Co-Director Bay Area Center for Physical Sciences and Oncology
University of California, San Francisco
San Francisco, California
- Seeking new strategies to prevent drug resistance and breast cancer metastasis.
- Laboratory studies are conducted to test a novel therapy to enhance response to chemotherapy.
- These pre-clinical studies may lead to clinical testing of a new approach that can improve outcomes for breast cancer patients.
Drug resistance is the leading cause of breast cancer metastasis and affects all of the sub-types of breast cancer. Dr. Weaver has identified a protein complex that protects tumor cells from the killing effects of chemotherapy. Her team developed a targeted therapy to block this protein and stimulate an anti-tumor immune response and is testing it in laboratory models.
Full Research Summary
Metastasis is the primary cause of breast cancer deaths and is typically a result of tumor resistance to therapy. Even breast cancers that initially respond to treatment, including targeted therapies such as Herceptin or anti-estrogen therapies, can relapse after initial response or ostensibly curative therapy.
Clearly, there is an urgent clinical need to develop strategies to prevent and overcome drug resistance and breast cancer recurrence.
Research has shown that an effective response to chemotherapy depends on the activation of an anti-tumor immune response triggered by stress. Inducing a stress response stimulates cancer cells to release factors that can directly retard tumor growth, reduce cancer cell survival to shrink the tumor, and stimulate anti-tumor immunity. Without this amplification response the chemotherapy is less effective, so residual cancer cells survive to metastasize and ultimately reduce patient survival.
Dr. Weaver’s team identified a protein complex NCoR2/HDAC3 that may play a role in driving drug resistance and metastasis by inhibiting the “stress amplification response” in cancer cells. To test this idea, they developed a therapy called “DECoR”, which targets cancer cells and specifically disengages NCoR2/HDAC3 complex and stimulate anti-tumor immunity. Laboratory studies have shown strong tumor shrinkage without side effects suggesting the “DECoR” strategy may have clinical potential.
Her BCRF research builds on these findings with the goal of moving the therapy into phase I clinical trials.
Dr. Weaver is currently the Director of the Center for Bioengineering and Tissue Regeneration in the Department of Surgery, and is a Professor in the Departments of Surgery, Radiation Oncology and Bioengineering and Therapeutic Sciences at UCSF in San Francisco, CA.
Dr. Weaver has over 20 years of experience in leading interdisciplinary research in oncology, including leadership of significant program projects including the Bay Area Physical Sciences and Oncology program and the UCSF Tumor Microenvironment Brain Program that merge approaches in the physical/engineering sciences with cancer cell biology and emphasize the role of the tumor microenvironment. Her research program focuses on the contribution of force, cell-intrinsic as well as extracellular matrix, to breast, pancreatic and glioblastoma tumor development and treatment. She also has an active research program exploring the interplay between cell and tissue level force and human embryonic stem cell differentiation.
Her education took place in Canada, with a bachelor’s degree in Chemistry from the University of Waterloo, an Honors Bachelor’s and PhD degree in Biochemistry from the University of Ottawa with a two-year postdoctoral training at the Institute for Biological Sciences, National Research Council of Canada and a 5-year postdoctoral tenure in Cancer Cell Biology at the Lawrence Berkeley National Laboratory at UC Berkeley with Dr. Mina J Bissell.
Dr. Weaver was recruited to the University of Pennsylvania in Philadelphia where she joined the faculty in the Department of Pathology as an Assistant Professor and was appointed a full member of the Institute for Medicine and Engineering. In mid-2006 she relocated to UCSF in San Francisco as an Associate Professor in the Department of Surgery with a joint appointment in Anatomy to take on the Directorship of the Center for Bioengineering & Tissue regeneration. She was invited to join the UCSF Cancer Center and Stem Cell Programs in 2007 and was cross appointed to the newly formed Department of Bioengineering and Therapeutic Sciences in 2008 and was promoted to full Professor in 2010.
Dr. Weaver has been recognized for her research and leadership through receipt of several awards including the DOD BCRP Scholar award in 2005 and the DOD BCRP Scholar expansion award in 20013 for exceptional creativity in breast cancer research and the ASCB WICB Midcareer award for sustained excellence in cell biology research in 2014. Most recently she was elected as the chair of the AACR TMEN working group in 2015 and she was elected to be a fellow of the American Society for Cell Biology in 2017.