A powerful new analytical tool offers a closer look at how tumor cells “shape-shift” to become more aggressive and untreatable, as shown in a study from researchers at Weill Cornell Medicine and the New York Genome Center.

A tumor cell shape-shifts by changing its cell type or state, thus altering its basic pattern of activity and perhaps even its appearance. This changeability or “plasticity” is a characteristic of cancer that leads to diverse tumor-cell populations and ultimately the emergence of cell types enabling treatment resistance and metastatic spread.

The new tool, described Sept. 24 in a paper in Nature Genetics, can be used to quantify this plasticity in samples of tumor cells. The researchers demonstrated it with analyses of tumor samples from animal models and human patients, identifying, for example, a key transitional cell state in glioblastoma, the most common form of brain cancer.

The FDA has approved a new targeted drug specifically for brain tumors called low-grade gliomas. The drug, vorasidenib, was shown in clinical trials to delay progression of low-grade gliomas that had mutations in the IDH1 or IDH2 genes.

“Although there have been other targeted therapies for the treatment of brain tumors with the IDH mutation, [this one] has been one of the most successful in survival prolongation of brain tumor patients,” said Darell Bigner, MD, PhD, the E. L. and Lucille F. Jones Cancer Distinguished Research Professor and founding director of the Preston Robert Tisch Brain Tumor Center at Duke.

In clinical trials, progression-free survival was estimated to be 27.7 months for people in the vorasidenib group versus 11.1 months for those in the placebo group.

Summary: Researchers found that mutations in the Sox3 gene cause hypopituitarism, a condition where the pituitary gland produces insufficient hormones, leading to growth issues and infertility. In a study on mice, they discovered that Sox3 mutations affect brain cells called NG2 glia, which are essential for hormone production.

Treating the mice with aspirin or altering their gut microbiome restored NG2 glia levels and reversed hypopituitarism. These findings suggest that both aspirin and gut bacteria could be explored as potential treatments for people with Sox3 mutations or other hormone-related disorders.