A menu of treatments for glioblastoma

Sara Piccirillo, PhD, is passionate about finding a way to beat glioblastoma, the most aggressive type of brain cancer. Although the median survival time has doubled since the 1990s, only 6% of those with glioblastoma survive five years or more after their diagnosis. Piccirillo thinks the way to fight glioblastoma lies in what makes it different from most cancers: the extreme differences among its tumor cells.

"Glioblastoma is the most aggressive brain tumor that we know about," she says. "There is very little in terms of effective treatment."

Glioblastoma rarely spreads beyond the brain but it can spread rapidly within the brain. Even if it initially responds to current therapies, Piccirillo says, it usually comes back and is often resistant to those therapies when it returns.

Originally from Milan, Italy, Piccirillo came to The University of New Mexico after a multi-year stop at the University of Cambridge. She joined the UNM Department of Cell Biology & Physiology and the UNM Comprehensive Cancer Center in early August 2019. The month before, Piccirillo had won the Gianni Bonadonna prize for new drug development, which is among Italy's most prestigious awards for young scientists. She will use the award to fund her research on glioblastoma treatment.

Piccirillo's research focuses on a feature of glioblastoma tumors that appears to be the source of their strength. As she explains, "They are extremely heterogeneous."

The cells in these tumors arise from multiple genetic changes, she says. Some cells may have different DNA mutations. Other cells may have extra copies of a gene. Still others may have chromosomes that have traded sections with each other. There are other types of changes as well, each of which may respond to a different treatment.

This mosaic of cells within glioblastoma tumors makes destroying them very difficult because some cells will respond to a given therapy but others won't. And those surviving cells, Piccirillo and her team believe, can restart the tumor. Even more troubling, some therapies can make cells resistant, so that when the tumor reforms, it is even more difficult to treat.

Piccirillo wants to first develop a catalog of cellular changes and the treatments that are most effective against each one. She then wants to turn that catalog into a menu that suggests combinations of glioblastoma treatments for different combinations of changes.

The menu idea is similar to a restaurant menu that suggests having broccoli with your steak but not with your chocolate dessert; some combinations are permitted, others won't be effective. Similarly, different people with glioblastoma might benefit from different combinations of treatments based on the changes found in their tumor cells. The menu would allow doctors to customize glioblastoma treatment to each person.

You need to have a smart way to combine therapies," Piccirillo says, "so that you can tackle the tumor but also avoid creating resistance."

Sara Piccirillo, PhD, The University of New Mexico

Piccirillo has amassed a collection of tumor samples and has begun compiling the many different cellular changes she finds within them. Once she and her team complete an initial version of the catalog, they will try different treatment combinations to find those that kill all the cancer cells. Although the treatment menu seems a long way off, Piccirillo is determined to improve the odds of beating glioblastoma.

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