Laboratory research on the genes that power cancer used to depend on cell cultures (think of those round, plastic Petri dishes from science class) or knockout mice (those with an inactive or "knocked out" gene that’s been replaced or disrupted with an artificial piece of DNA). But cells cultured on plastic don’t behave like cells in living organisms. Knockout mice take about a year to develop for each different gene mutation. And if you get negative results, it takes another year for the next try at a different gene. Researchers at Huntsman Cancer Institute (HCI) have developed a unique mouse model that makes studying genetic factors in cancers within the living organism much quicker and more flexible.

“With this model, we can identify the mutations found in patients’ tumors, make those mutations in the lab, and introduce them into a mouse through a virus designed to create a melanoma tumor that faithfully mimics the human disease within a few weeks,” says Matthew VanBrocklin, PhD, an HCI investigator and assistant professor in the Department of Surgery at the University of Utah.

In 2013, VanBrocklin received a five-year grant from the National Cancer Institute to investigate the role of a gene called c-KIT in the development and progression of melanoma using this mouse model. The research will also examine other genes that may enhance c-KIT’s action.

The tumors in about 50% of melanoma patients have mutations in a gene called BRAF. The c-KIT gene mutations are associated with a smaller percentage of aggressive melanoma subtypes, including those related to chronic sun-damaged skin.

“Because the mutation has been found in these tumor cells, people have assumed that it’s relevant, but the details of its role have never been directly addressed,” says VanBrocklin. “Strong evidence one way or the other isn’t yet available. We’re setting out to find that strong evidence.” The overall goal is to develop new, more effective treatments for patients whose melanoma tumors have c-KIT mutations.

New discoveries about c-KIT are only one of the possibilities for cancer research using VanBrocklin’s mouse model.

For example, melanoma therapies that target BRAF have given a phenomenal response, but patients often develop resistance to these therapies and the cancer progresses. “Perhaps other pathways are activating that allow the cancer to progress even though BRAF is blocked. Maybe there’s another point downstream in the BRAF pathway that activates to keep the cancer going,” says VanBrocklin. “Now we can investigate why resistance occurs and discover new therapies that target alternate pathways much more rapidly and at much less cost.”

The VanBrocklin Lab is working to apply this modeling technique to other cancers. “We’re still in the designing steps. No one has done this before. It’s exciting work.”

Learn more about melanoma, including risk factors and screening. Or visit our Melanoma and Cutaneous Oncology Program webpages.