Brain cancer is on higher on the discussion list this week after news broke of Senator John McCain’s recent glioblastoma diagnosis. The news remind us of that cancer doesn’t discriminate, and that we are all fallible. But, instead of being frightened, let’s talk about what some scientists are doing to better understand and treat this infamous disease.
At a cancer laboratory at Case Western Reserve University, a team of scientists, led by Drs. Jeremy Rich and Paul Tesar, is uncovering the genes that enable brain tumors to thrive. Knowing these genes, they reasoned, could give us the precise targets to stop their growth and extend survival.
The team began with human glioblastoma cells which they either maintained in a dish, or transplanted into mice to mimic natural tumor biology. They then profiled the genes in the two tumor environments to pinpoint those that are essential to tumor survival. This led to the identification of 57 genes that differed between the two environments. This 57 genes seemed to be involved in the animal model of the brain tumor, suggesting 57 new targets at which to aim.
"There was very little overlap of the targets identified in the new in vivo screening method and the traditional cell culture screen," said Dr. Jeremy Rich, the study’s co-senior author, who is now a professor at the University of California San Diego. "This means the field has been missing a number of potential therapeutic targets that may actually improve patient outcomes and prolong survival."
Further investigation into the 57 genes revealed that 12 of the genes are involved with how cancer cells respond to stress. When genes in this pathway were inhibited, the mice had extended survival while tumor cells in culture showed no effect.
"Our study found that in a natural environment, tumor cells are more susceptible to inhibition of their stress response mechanisms,” said Dr. Tyler Miller, the study’s first author. “Current chemotherapies all target proliferating, or dividing cells. We know that type of therapy doesn't work for glioblastoma. Our findings suggest that targeting the stress response may be better at slowing tumor growth than targeting cell proliferation, which opens up a new avenue for therapeutic development."
Glioblastoma is often nicknamed “octopus tumor” because the malignant glial cells form vast networks of tendrils throughout the brain. This makes it extremely difficult to completely get rid of the tumor. As such, the brain cancer can evade even the most aggressive surgeries, chemotherapies, and radiotherapies, leaving patients with a five-year survival rate of less than 10 percent. Over 70 percent of patients diagnosed with this type of brain cancer rarely survive past the two-year mark.
"Prior attempts at discovering therapeutic targets have generally been done in cell culture, that is, patient cells on plastic dishes in artificial media to help them grow. The hope is that systems like ours that more closely mimic the natural tumor environment will identify new targets that better translate into effective therapies for patients,” said Dr. Paul Tesar, a distinguished professor at Case Western University School of Medicine, and the study’s other co-senior author. Indeed, the team hopes their approach will shed more light on how to treat this cancer and other cancer types as well.
Additional sources: Case Western Reserve University