Thursday, October 29, 2020

Combination Of Two Clinically Approved Drugs Cause Brain Tumor Cells To Eat Themselves

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It has been observed that people prescribed antidepressants curiously have a lower incidence of one of the most common, and most aggressive, types of brain tumor. Glioblastomas account for around 15% of all primary brain tumors, and the survival rate is not good, often measured in months rather than years. But new research has shown that by combining a specific type of antidepressant with another drug, this time a blood thinner, it is possible to slow the progression of glioblastoma in mice.

“We were interested in exploring clinically approved drugs,” Douglas Hanahan, who led the study published in Cancer Cells, told IFLScience, “so if we found anything interesting we can potentially incentivize clinical evaluation, and in a reasonable period of time. Because the time line from new drug to clinical approval can take a decade or more.”

They decided to focus on the “cellular recycling system” of cells, which is known as autophagy (literally “self-eat”). This is where stressed cells recycle some of their cellular components in order to survive in conditions of, for example, nutrient limitation. Autophagy can be beneficial to a cell, but only in low levels.

They found that a specific type of antidepressant, called tricyclic antidepressants, increased autophagy in glioblastoma tumors. But when tested in mice, it only demonstrated limited effects.

Spurred on by this anyway, they decided to screen other clinical drugs and came across a blood thinner that also affected this recycling system. Separately, both these drugs increased this process a little, but not enough to cause damage. Together, however, they seemed to push the cells over a threshold, effectively making the tumor cells eat themselves to death.

“Both drugs were acting on an intracellular pathway that regulates the autophagy,” explained Hanahan. “They affect a signalling molecule called cyclic AMP, and both of these drugs were working together to increase the production of cyclic AMP, which in turn increased the rate of autophagy. The data suggests that this rate of autophagy went over a threshold of viability.”

Even though the combination of drugs encouraged some tumor cells to eat themselves, the therapy wasn’t able to cure the cancer because tumors aren’t homogenous, or the same throughout. Instead, the drugs slowed the tumor’s progression and modestly expanded the lifespan of the mice.

What’s exciting about this research is that both these drugs are relatively inexpensive, and already clinically proven. There are even some reports of people taking both medications at the same time, implying that they can work together without side effects, though Hanahan hopes that this research will encourage proper clinical trials in humans.

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