New gene therapy stops spread of deadly cancer cells, study shows

According to the study, these metastatic cancer cells are responsible for 90% of cancer deaths. By silencing this gene in lab models of cancer, the treatment successfully prevented metastatic cells from growing. The findings could lead to new strategies to treat metastatic cancer and would be particularly impactful for patients with pancreatic cancer.

“Our results point to potentially novel therapeutic avenues to specifically target metastatic cancer,” said senior author Raul Mostoslavsky, MD, PhD, who is the scientific director of the Krantz Family Center for Cancer Research at the Mass General Cancer Center.

Mostoslavsky and his team started by comparing gene expression in primary and metastatic tumors in mice with pancreatic or breast cancer. After identifying various genes whose expression increased in metastatic tumor cells, the researchers silenced each gene individually.

When they blocked the Gstt1 gene, it didn't affect primary tumor cells in mice but stopped metastatic cancer cells from growing and spreading. This effect was also observed in human pancreatic cancer cell lines derived from metastatic tumors.

The Gstt1 gene produces an enzyme that belongs to a large family of proteins known for protecting cells from toxins and other functions. Further studies showed that this enzyme enables metastatic cancer cells to alter and release a protein called fibronectin, crucial for cell attachment to the extracellular matrix, which supports and structures cells and tissues.

“Gstt1 alters the matrix surrounding the metastatic cells so they can grow in these foreign niches,” said Mostoslavsky. “Our results could lead to new strategies for the treatment of metastatic disease. This would be especially impactful for pancreatic cancer, in which most patients present with metastases when initially diagnosed.”