Daniel and Martina Lewis Chair, Gene Expression Laboratory
The Salk Institute
La Jolla, California
Area of Focus: Tumor Biology
- Seeking new preventive and therapeutic strategies for aggressive disease.
- Sophisticated laboratory studies are ongoing to identify cell types that drive tumor behavior and to understand the communication that takes place between cancer cells and normal cells.
- These studies are yielding new ideas for treatments to target the cancer cells that are responsible for drug resistance and tumor progression.
Breast cancer is not a single disease, but a group of diseases characterized by different physical and molecular features. Even a single breast tumor is made up of tumor cells with very different molecular features that drive their behaviors, such as how they respond to treatment, whether they can invade tissue, or travel to other parts of the body. This is particularly true in triple negative breast cancer (TNBC) and is a major factor underlying the aggressive and drug resistant nature of TNBC. Dr. Wahl is conducting laboratory studies aimed at identifying the drivers of this intratumoral cellular diversity and strategies to improve outcomes for patients with TNBC.
Full Research Summary
Dr. Wahl’s BCRF research is focused on understanding the properties of stem-like cells in triple negative breast cancer (TNBC), a very aggressive type of breast cancer. One problem in treating patients with TNBC is tumor heterogeneity, which is the presence of many different types of cancer cells within a single tumor. This makes treating the tumor difficult because not all the tumor cells respond to therapy the same way.
One factor that appears to contribute to this involves the ability of the cells to change their state, like a chameleon can change colors. The basic processes that enable a cancer cell to change state remain largely unknown. A recent discovery from Dr. Wahl’s laboratory is a gene that causes triple negative breast cancer cells to become mobile and travel to other parts of the body.
Particularly important is whether factors that contribute to breast cancer risk, like obesity, act in part by facilitating the ability of the cancer cell to change its properties and to become more dangerous in the process. Dr. Wahl’s group has developed a unique way to see the cells in tumors as they change state. This year, Dr. Wahl will collaborate with BCRF colleague, Andrew Dannenberg to study the effects of obesity on cell state changes in the normal mammary gland and in mammary glands containing cancer-causing mutations.
Dr. Geoffrey M. Wahl is a Professor at the Salk Institute, an Adjunct Professor at the University of California, San Diego in the Department of Biology, and the past President of the American Association for Cancer Research (2006-2007). Dr. Wahl’s research focuses on the cells that originate and perpetuate cancers, the conditions that lead to cancer progression and metastasis, and why tumors become therapy resistant. Dr. Wahl’s early work involved uncovering the mechanisms that lead to the most common forms of genetic instability in human cancers, including those often seen in the highly aggressive, basal-like group of triple negative breast cancers. BCRF funds have been used to discern the nature of the cells that originate or perpetuate basal-like breast cancers. The Wahl laboratory found that mutations in the p53 gene, the most commonly mutated gene in basal-like breast cancer, increases the chances that a fully mature cell can “reprogram” into a more primitive “stem-like” cell. His lab also found that these primitive cells have strong similarities to the earliest stem cells identifiable during breast development, which they call fetal mammary stem cells. BCRF funding is enabling Dr. Wahl’s team to characterize the pathways essential for the growth and survival of these cells, as he expects these pathways will be important for perpetuation of basal-like breast cancers. The Wahl lab is also identifying molecules useful for tracking these cells in the body. Their hope is that these approaches will lead to development of new molecularly targeted therapeutics and diagnostic tools to provide alternatives, or additions, to chemotherapy, currently the only type of drug therapy for patients with triple negative breast cancer.