Skin Cancer Research Highlights

Grantee: Weiguo Cui, PhD
Institution: Medical College of Wisconsin in Milwaukee
Area of Study: Leukemia, Immunology, and Blood Cell Development
Grant Term: 1/1/18 to 12/31/21

The Challenge: Immunotherapy uses a patient’s own immune system to fight cancer. Certain types of immunotherapy known as cell therapy or cell transfer therapy, use immune cells called T cells, which are a type of white blood cell. The patient’s T cells are genetically changed in a lab to make them better able to kill cancer cells and returned to the patient’s body. But these superpowered T cells don’t work at full speed forever. They gradually become exhausted, and their cancer-killing abilities weaken.

The Research: Weiguo Cui, PhD, and his team on working on immunotherapy for melanoma. They believe they’ve found a genetic pathway that controls the T cells’ “killing” strength and duration. Using mice that have melanoma, Cui and his team are studying the pathway and hope to use it to design new ways to reprogram the exhausted T cells, thereby allowing them to regain and keep their “super-killing” abilities. 

The Goal and Potential Long-Term Benefits: Cui’s team is hopeful that their work in mice will eventually lead to new immunotherapy treatments that target different types of cancer cells.

Grantee: Eva Hernando, PhD
Institution: New York University School of Medicine in New York City
Area of Study: Cell Structure and Metastasis
Grant Term: 1/1/20 to 12/31/22

The Challenge: In some cases, melanoma can spread, or metastasize, to the brain. Researchers don’t fully understand how melanoma cells travel to and grow in the brain to form new tumors. Currently, there are few treatments available for brain metastasis. 

The Research: While studying a melanoma tumor that had metastasized and formed in the brain, Eva Hernando, PhD, and her team discovered something unexpected. They found unusually high levels of proteins that are related to Alzheimer’s disease, including one called amyloid processing protein (APP).

Normally, APP plays a role in nerve function of many tissues and organs throughout the body. But certain changes that can happen in APP have been linked to Alzheimer’s disease. Hernando’s team found that APP is also essential for melanoma cells to adapt to the brain.

Hernando is studying:

• How APP affects melanoma growth in the brain.
• Whether treatments that focus on APP could work for melanoma in the brain by testing substances in mice that are already being tested in Alzheimer’s patients.
• Whether brain metastases from other types of cancer, such as lung and breast cancer, need APP to grow. 

The Goal and Long-term Possibilities: As soon as Hernando’s team finishes their mice studies, they hope to rapidly start testing it in people who have melanoma brain metastases, since the substances involved have already been through safety testing in humans. If this work is successful, it may change how brain metastases are treated and may improve the outcomes of people with certain types of metastatic tumors.  

Grantee: Peter A. Kanetsky, PhD, MPH
Institution: H. Lee Moffitt Cancer Center and Research Institute, Inc in Tampa, FL
Area of Research: Cancer Control and Prevention:  Health Policy and Health Service
Grant Term: 1/1/15 to 12/31/20

The Challenge: Skin cancer can be diagnosed in anyone, and it’s pretty well known that people with light-colored skin that freckles or burns easily are at increased risk for skin cancer, including melanoma. In previous research, Peter Kanetsky, PhD, MPH, found that people who have inherited certain changes or mutations in a gene called MC1R also have a higher risk of getting melanoma—even if they have darker skin and don’t burn quickly in the sun. The challenge is that they may not realize their risk.  

The Research: Kanetsky and his team wanted to know if telling people who have the MC1R mutation, about their increased risk for melanoma would it motivate them to better protect themselves from the sun.

As the leader of a clinical trial, Kanetsky tested participants for the gene variation and gave them a survey to learn about their concerns about developing melanoma and about how they had protected themselves and their children from the sun.

Then they randomly divided participants into two groups. They gave one group general information about how to reduce the risk of melanoma risk. The other group received personalized information about their specific risks, including whether they had the MC1R gene mutation.

All participants took the survey again at the end of the trial and 6 months and 1 year after it.

Kanetsky is now examining the results to see if receiving personalized information changed the behavior of people with the MC1R gene mutation. He’s specifically looking how whether they took more precautions to protect themselves and their children from the sun.

The Goal and Long-term Possibilities: Kanetsky’s goal is to help more people—especially those with a high risk —understand their risk--and protect their skin from UV radiation to reduce the number of new cases of melanoma. He also wants to help more people survive melanoma by promoting early detection and treatment. 

Learn more about Dr. Kanetsky’s work.

Grantee: Richard Wang, MD, PhD
Institution: University of Texas Southwestern Medical Center in Dallas
Area of Research: Tumor Biochemistry and Endocrinology
Term: 7/01/2018 to 06/30/2022

The Challenge: Most cells need sugar (glucose) to function well because glucose gives them energy to do their work. Cancer cells are no different. They use a lot of sugar when they’re growing and spreading. This is also true for squamous cell skin cancer, the second most common form of skin cancer.

Research shows that a protein called GLUT1 acts like a food delivery truck. It transports glucose into a cell so it can be used for energy, keeping the cell healthy.

When cancer cells develop, they hijack the GLUT1 delivery system and gobble up glucose near them to get the energy they need to survive and grow. Scientists have found that stopping this process helps to starve cancer cells. But the problem is that it usually starves normal cells, too, which can be dangerous. So some studies suggest stopping the GLUT1 delivery system may not be an effective treatment for cancer. 

The Research: In previous studies, Richard Wang, MD, PhD, and his team were surprised to discover that normal skin cells don’t need GLUT1 when they are developing. This finding led them to wonder if stopping the glucose transport process could prevent squamous cell skin cancer from developing without harming healthy skin cells.

Wang’s team is testing several drugs on the skin of mice with squamous cell skin cancer. The drugs, called GLUT1 inhibitors, help stop glucose from getting into the cancer cells while having limited effects on normal cells. The researchers are also testing how GLUT1 inhibitors work when combined with existing types of chemotherapy. 

The Goal and Long-term Possibilities: Wang hopes to show that stopping glucose transport can become a new treatment approach for skin cancer. He believes his work could also help scientists better understand the abnormal metabolism of all types of cancer.