Daniel and Martina Lewis Chair, Gene Expression Laboratory
The Salk Institute
La Jolla, CA
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.
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 the cells do not all respond to therapy the same way.
Stem cells are the cells from which tissues are derived during embryonic development and are required to replace tissue after injury. Dr. Wahl's team identified similarities in some TNBC cells and mammary stem cells (MaSC), which could explain the aggressive behavior of these cancers. These may also be the cells that cause tumors to become resistant to drugs and spread to other organs.
His team is characterizing these cells further to identify molecular targets for the development of new therapeutics that can provide an alternative to, or be used in combination with, chemotherapy in patients whose cancers show the MaSC signature.
Over the next year, they will employ sophisticated methods to determine when the stem-like cells arise during tumor development and how cancer cells communicate with the normal cells with which they interact.
The team expects that this new information will lead to better therapies based on knowledge of the genes expressed in different cell types in each individual tumor.
The complexities of cancer have been obscured by studying the tumor as a whole. This new approach will enable analysis of the individual parts of which the whole is composed.
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.