Cancer patients may soon have better therapy options, suggests a recent study.
Researchers from Case Western Reserve University School of Medicine and The Cleveland Clinic designed a way to screen brain tumour cells and identify potential drug targets missed by other methods. The team successfully used their technique to find a glioblastoma cancer gene that, when blocked, extends mouse survival rates.
The team implanted patient-derived glioblastoma cells in mice and measured gene activity in the growing brain tumours. They compared the gene activity to that of cancer cells grown in vitro--inside laboratory dishes. The researchers found 55 genes required for the cells to grow inside working brains--in vivo--but not inside laboratory dishes.
"The genes needed for cancer cells to survive in a tumour were not necessarily the same ones needed to survive in a Petri dish," said first author Tyler Miller. "This means the field may have been missing a whole host of potential therapeutic targets that may actually improve patient outcomes and prolong survival." Glioblastoma is associated with a 2-3 year survival rate and few meaningful treatment options, according to the American Brain Tumour Association.
The high-throughput screening technique revealed new vulnerabilities in glioblastoma tumours that could be targeted by drug developers. Of the 55 genes identified, 12 were all related to a single process--how cancer cells respond to stress. The researchers blocked one of the stress genes in the implanted tumours and the mice lived longer. But blocking the gene inside laboratory dishes did not alter glioblastoma cell growth or survival.
Miller said, "Our study found that in a natural environment, tumour cells are more susceptible to inhibition of their stress response mechanisms. Current chemotherapies all target proliferating, or dividing cells. That doesn't always work for glioblastoma. Our findings suggest that targeting the stress response may be better at slowing tumour growth than targeting cell proliferation, which opens up a new avenue for therapeutic development."
The study is published in Nature.