Specialized Program of Research Excellence (SPORE) in Breast Cancer
The University of Chicago Specialized Program of Research Excellence (SPORE) in Breast Cancer brings together a multidisciplinary team of basic, clinical, and population science investigators to design innovative research and use a global strategy to reduce worldwide suffering from breast cancer. Our program is 1 of only 11 NCI Breast Cancer SPOREs in the United States.
The UChicago Breast Cancer SPORE aims to develop genetic and imaging-based approaches to the prevention, detection, and treatment of breast cancer in women who are at increased risk of developing an aggressive form of malignancy at a young age. Since this type of breast cancer disproportionately affects young women of African ancestry, a portion of the Breast SPORE tackles the global issue of health disparities among various ethnic and racial groups.
The Breast Cancer SPORE comprises four primary research projects, which are supported by three resource cores. In addition, the Developmental Research Program and the Career Development Program promote novel research endeavors and provide support for young investigators at the University of Chicago.
Principal Investigator Olufunmilayo Olopade, MBBS
- "Cancer Knows No Borders" article in The Scientist magazine (Word doc)
- Dr. Funmi Olopade to be awarded 2013 Scientific and Medical Award of Distinction by the Susan G. Komen for the Cure (PDF)
UChicago Breast Cancer SPORE Overall Research Strategy
Projects and Specific Aims
Project 1: Complex Personalized Cancer Risk Profiles in Diverse Populations.
Project Leaders: Olufunmilayo Olopade, MBBS, Dezheng Huo, PhD, Linda Patrick-Miller, PhD
Co-Investigators: Habib Ahsan, MBBS, Angela Bradbury, MD, Nancy J. Cox, PhD, Peter Hulick, MD, Katharine Yao, MD
Hypothesis: We hypothesize that genomic markers influence breast cancer risk, and population-specific Polygenic Risk Score (PRS) can be used to stratify diverse populations of women into risk categories and that provision of information
regarding complex genetic risks will positively influence behavior and cancer prevention activities.
Specific Aim 1: Evaluate the performance of PRS in clinically defined cohorts of high-risk women.
Specific Aim 2: Assess stakeholder (patient and provider) preferences, and evaluate the risks and benefits of communicating Complex Personalized Cancer Risk Profiles to ethnically diverse high-risk patients.
Project 2: Targeting Heat Shock Protein 90 Client Proteins in Triple Negative Breast Cancer
Project Leaders: Suzanne Conzen, MD, Olufunmilayo I. Olopade, MBBS, Rita Nanda, MD
Co-Investigators: Gini Fleming, MD, Nora Jaskowiak, MD
Hypothesis: We hypothesize that inactivating the Hsp90 client proteins GR/SGK1 and JAK will increase TNBC chemotherapy sensitivity and tumor responsiveness.
Specific Aim 1: Determine if inactivation of the GR/SGK1 pathway mediates Hsp90-inhibitor-induced TNBC tumor cell death.
Specific Aim 2: Determine if inactivation of the JAK/STAT pathway mediates Hsp90-inhibitor-induced TNBC tumor cell death.
Specific Aim 3: Determine whether GR/SGK1 and/or JAK/STAT3 expression in TNBC decreases following neoadjuvant treatment with an Hsp90 inhibitor.
Project 3: Mechanisms of Immune Evasion in Breast Cancer
Project Leaders: Yang-Xin Fu, MD, PhD, Rita Nanda, MD
Co-investigators: Thomas Gajewski, MD, PhD
Hypothesis: We hypothesize that anti-PD-L1 can overcome Ab-resistance and lead to tumor regression.
Specific Aim 1: Determine if and how anti-PD-L1 antibody synergizes with anti-neu antibody treatment.
Specific Aim 2: Understand the role that PD-L1 upregulation plays in response to trastuzumab-based therapy in patients with HER2-amplified breast cancer.
Project 4: Pharmacogenomics of Breast Cancer Therapies
Project Leaders: M. Eileen Dolan, PhD, Peter O’Donnell, MD, Gini Fleming, MD
Co-Investigator: Nancy J. Cox, PhD, Douglas Merkel, MD, Mark Ratain, MD
Hypothesis: We hypothesize that germline genetic variation accounts for a significant proportion of the inter-individual variability in the toxicity of chemotherapy agents used in breast cancer therapy, and that provision of information regarding
genetic risks for toxicity to clinicians will alter and increase the chemotherapy treatment choices for patients.
Specific Aim 1: Identify a set of SNPs associated with capecitabine and paclitaxel toxicity in preclinical models, including characterization of these variants using pre-clinical functional studies.
Specific Aim 2: Use five large sets of clinical samples from breast cancer patients treated with paclitaxel or capecitabine to: a) validate LCL toxicity associated SNPs from Aim 1; b) identify novel genetic variants associated with paclitaxel- or capecitabine-related toxicity, and; c) build multigenic predictive models associated with sensitivity to paclitaxel and capecitabine.
Specific Aim 3: Translate well-characterized variants from the above clinical studies of breast cancer pharmacogenomics into a clinical, preemptive testing treatment approach for breast cancer patients.