Pathogenesis
The underlying cellular, genetic, and biological processes of breast cancer continue to be major topics of research interest and CBCRP funding for 2001. There remains much we do not know about the development, progression, and spread of breast cancer. Why do cancer cells have the ability to divide beyond the point when normal breast cells become limited? What is the underlying biology that explains why drugs used for treatment don't work very well or stop working after initial success in a patient? What is the total number of critical breast cancer genes, and what can this tell us about the best clinical treatment options? Basic researchers are working with an increased appreciation of the complexity of the actual disease, and they are more aware of the concerns of women being diagnosed with breast cancer.
Some of the topics in this area the CBCRP funded in 2001 include:
- Apoptosis. The process of programmed cell death that often becomes defective in breast cancer and allows tumors to survive drug treatment and the immune response.
- Angiogenesis and the tumor microenvironment. How breast cancers differ from normal breast cells in stimulating blood vessel growth, attachment events, cell movement, and invasion properties.
- Cell growth. Why breast cancer cells divide in an uncontrolled manner, especially through the Her-2 (ErbB2) oncogene and estrogen receptors.
- Genetic defects. Why gene mutations accumulate during breast cancer progression and are either not repaired or recognized.
- Model systems and technology. The use of lower organisms for genetic studies and new technologies, such as DNA array (gene chips), for rapid analysis of multiple genes and proteins of interest for breast cancer.
To study breast cancer, researchers use sophisticated tools to detect previously unknown genes and the factors that cause defects in the regulation of known genes. The intricate protein pathways inside breast cancer cells are dissected, the breast cancer cells are experimentally modified, and breast cancer growth and spread are studied in cell and animal models.
The recent success of the Human Genome Project to identify the 30,000+ human genes has provided us the ‘pieces of the puzzle,’ but clinicians and basic researchers must assemble these pieces into a coherent picture of breast cancer. How might this happen? Current thinking is that breast cancer is actually not one disease, but a group of genetically different diseases. Work is in progress to define these distinct clinical subsets based on discrete differences in genes and proteins found in each woman's breast cancer. This has implications for basic research, too. In the near future, hopefully, we will see a better integration of basic research model systems that more closely replicate the ‘real world’ clinical situation.
Role of PTEN/Akt Pathway in Invasion in Human Breast Cancer
Bose, Shikha
Cedars-Sinai Medical Center
1 year, $100,000
Molecular Study of BAG Domains:A New Motif in Breast Cancer
Briknarova, Klara
The Burnham Institute
2 years, $86,400
Trypsin-like Proteases as Metastatic Agents in Breast Cancer
DeFea, Kathryn
University of California,Riverside
3 years, $295,980
Role of Id-2 in Breast Cancer and its Relationship to Id-1
Desprez, Pierre-Yves
California Pacific Medical Center Research Institute
2 years, $296,541
The Role of BRCA1 in Nucleotide Excision Repair
Hartman,Anne-Renee
Stanford University
2 years, $86,400
The Role of SGK in Breast Cancer Proliferation
Hayashi, Masaaki
Scripps Research Institute
2 years, $86,400
Lasp-1 Signaling in Breast Carcinoma Cell Invasion/Migration
Lin, Yi Hsing
Scripps Research Institute
2 years, $86,400
The Functions of BRCA2 in Repairing DNA Damage
Lio, Yi-Ching
Lawrence Berkeley National Laboratory
3 years, $495,388
Tax Check-off Grant
Genes That Modulate Dioxin-Induced Breast Cancer
Lu, Quan
Stanford University
2 years, $86,400
Genetic Analysis of ErbB Signaling in C.Elegans
Moghal, Nadeem
California Institute of Technology
2 years, $86,400
Tax Check-off Grant
Smoking Effect on Lung Metastasis from Breast Cancer
Murin, Susan
University of California, Davis
1.5 years, $75,000
(Co-funded with the Tobacco-Related Disease Research Program)
Tumor Suppression by Dystroglycan in Breast Epithelial Cells
Muschler, John
Lawrence Berkeley National Laboratory
2 years, $328,214
Rodent Model for Human Ductal Carcinoma in Situ
Nandi, Satyabrata
University of California, Berkeley
1 year, $100,000
Molecular Characterization of ErbB2 Positive Breast Cancers
Neve, Richard
Buck Institute for Age Research
2 years, $86,400
SBP-1: A Novel Survivin Binding Protein in Breast Cancer
Okada, Kazuya
The Burnham Institute
2 years, $86,400
P132Cas and Antiestrogen Resistance of Breast Cancer
Rehn, Marko
The Burnham Institute
2 years, $86,400
Novel Enzymes Associated with Breast Cancer Angiogensis
Rosen, Steven
University of California, San Francisco
1.5 years, $100,000
Are EGF-Receptors Activated by IL-8 in Breast Cancer?
Schraufstatter, Ingrid
La Jolla Institute for Molecular Medicine
1 year, $155,475
Pathway-Specific Gene Expression in Breast Cancer Cells
Sweeney, Colleen
University of California, Davis
3 years, $299,287
Overcoming Drug Resistance in Breast Cancer
Vuori, Kristiina
The Burnham Institute
2 years, $386,457
Regulation of the ATR Checkpoint Response in Breast Cancer
Yean, Dawn
Stanford University
2 years, $86,400
