The next generation of melanoma therapies will be driven by the basic science that underlies melanoma biology. Wistar’s Melanoma Research Center takes a comprehensive approach to understanding these basic mechanisms, and uses that knowledge in partnership with clinicians to create new therapeutics and preventative strategies.
The 5-year goal of the Center is to delineate the different types of melanoma. Each type of melanoma and each individual tumor have unique genetic and biologic signatures that researchers must understand to best tailor new strategies for eliminating all tumor cells.
There are five parts of this overall strategy:
Melanoma, like all cancers, is primarily a genetic disease. While some people do have an inherited predisposition to developing melanoma, most acquire mutations from exposure to the sun and ultraviolet light. Wistar Melanoma Research Center scientists seek to identify how individual mutations may cause melanocytes to become cancerous or how acquired mutations may allow normal tumor cells to resist treatment.
Of course, genes do not work in isolation. All cells, cancerous or not, function through complex networks where genes and proteins relate to each other, either through direct contact or chemical signals. These networks, or pathways, can regulate how specific genes are turned on or off. They can also be a factor in driving – or stopping – melanoma.
The Wistar Institute Melanoma Research Center will use this information to:
- Inhibit pathways that drive melanoma
- Collaborate with industry to test new drugs that may serve as inhibitors
- Disrupt melanoma signaling by developing a new generation of inhibitors in-house
- Identify subpopulations of melanoma cells that require specific targeting and develop strategies for dual therapies targeting the various subpopulations.
- Test combinations of inhibitors in novel cell and animal model systems.
Wistar scientists believe that combination therapy, in particular, may be an important tool for treating the disease. Melanoma can appear to be an expert at manipulating pathways, so a single inhibitor may serve as a roadblock only temporarily, and the cells will eventually find another route to survival. Setting up many such “roadblocks” at once could cut off any chance melanoma cells have to escape therapy.
Much like cancer itself, there is not one single type of melanoma. Knowing more about a patient’s particular type of melanoma will help physicians better understand how to treat the disease. Fortunately, melanoma provides clues in the form of biological markers, or biomarkers.
Biomarkers can be as simple as a molecule shed by a tumor into the bloodstream or as complicated as a pattern of “gene expression” – a profile determining which genes are turned on or off – taken from a tumor biopsy.
Scientists at the Melanoma Research Center are identifying and developing new biomarkers that physicians use for detection, risk assessment, therapy selection and long-term monitoring of disease recurrence.
The human immune system is a powerful network of cells and systems evolved to prevent infection from taking hold and to destroy aberrant cells. However, sometimes the immune system may need a little help in directing its resources. The Melanoma Research Center is actively developing strategies to strengthen the immune response to melanoma, whether through cancer vaccines or therapeutics.
The best way to fight melanoma is to prevent it from developing in the first place. The Melanoma Research Center is studying the specific mechanisms by which intense, intermittent sun exposure leads to melanoma. This work includes:
- Understanding whether stem cells in skin are the target for transformation to melanoma.
- Characterizing the very first steps in melanoma development versus mole formation and identifying the risk factors that can lead to malignant transformation.
- Developing new models that mimic melanoma development in humans and beginning experimental trials for prevention.