PHILADELPHIA (October 15, 2021)—Recent findings from a study conducted at Fox Chase Cancer Center could help pave the way for more effective treatment of aggressive brain tumors, researchers say.
The work was conducted by a team led by Zeng-jie Yang, MD, PhD, an associate professor in the Cancer Signaling and Epigenetics Program. The project focused on glioblastomas, which are very malignant brain tumors for which treatment options are limited.
The most promising finding is that reducing nestin, a common molecular marker in cancer cells, in glioblastoma cells made them more sensitive to a particular class of drugs that disrupt proteins called tubulins. Yang’s lab is currently working towards a method to target nestin, which would make these tubulin drugs more effective in treating glioblastomas.
Yang’s team found that nestin is present at very high levels in glioblastomas. Yang, who is also a neurosurgeon, believes this research has immediate implications for treatment. “During diagnosis, if a pathologist finds the tumor cells highly express nestin, it may mean that these cells are more resistant to the tubulin drugs, or conversely, if they do not express nestin, they may be more susceptible to the drugs,” Yang said.
The researchers also looked at how nestin affected tumor growth in live animals. They transplanted cancer cells from glioblastomas into live mice; the transplanted cells led to the growth of large tumors and premature death. When nestin-deficient cancer cells were transplanted into the mice, the resultant tumors were much smaller and the mice lived longer.
The collaborative environment at Fox Chase was instrumental in the success of this project, Yang said. Although his group found that they could prevent the growth of glioma cells by reducing nestin, the specific cause of this slowed growth was initially a puzzle.
That is until Tim J. Yen, PhD, a professor in the Cancer Signaling and Epigenetics Program, helped identify the molecular defects present in the nestin-deficient cells. With Yen’s help, the team found that these cells did not properly form spindles, which are tubulin-derived structures that control cell division. The research team further demonstrated that nestin interacts with tubulins in this spindle, which led to the discovery that nestin makes glioblastomas sensitive to tubulin drugs.
The study, “Nestin Is Required for Spindle Assembly and Cell-Cycle Progression in Glioblastoma Cells,” was published in Molecular Cancer Research.